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Retinal Degenerative Diseases XIX

John Ash
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Advances in Experimental Medicine and Biology 1415

John D. Ash · Eric Pierce · Robert E. Anderson ·


Catherine Bowes Rickman · Joe G. Hollyfield ·
Christian Grimm Editors

Retinal
Degenerative
Diseases XIX
Mechanisms and Experimental Therapy
Advances in Experimental Medicine
and Biology

Volume 1415

Series Editors
Wim E. Crusio, Institut de Neurosciences Cognitives et Intégratives
d’Aquitaine, CNRS and University of Bordeaux, Pessac Cedex, France
Haidong Dong, Departments of Urology and Immunology, Mayo Clinic
Rochester, MN, USA
Heinfried H. Radeke, Institute of Pharmacology and Toxicology, Clinic of
the Goethe University Frankfurt Main, Frankfurt am Main, Hessen,
Germany
Nima Rezaei, Research Center for Immunodeficiencies, Children’s Medical
Center, Tehran University of Medical Sciences, Tehran, Iran
Ortrud Steinlein, Institute of Human Genetics, LMU University Hospital
Munich, Germany
Junjie Xiao, Cardiac Regeneration and Ageing Lab, Institute of
Cardiovascular Sciences, School of Life Science, Shanghai University
Shanghai, China
Advances in Experimental Medicine and Biology provides a platform for
scientific contributions in the main disciplines of the biomedicine and the life
sciences. This series publishes thematic volumes on contemporary research in
the areas of microbiology, immunology, neurosciences, biochemistry,
biomedical engineering, genetics, physiology, and cancer research. Covering
emerging topics and techniques in basic and clinical science, it brings together
clinicians and researchers from various fields.
Advances in Experimental Medicine and Biology has been publishing
exceptional works in the field for over 40 years, and is indexed in SCOPUS,
Medline (PubMed), EMBASE, BIOSIS, Reaxys, EMBiology, the Chemical
Abstracts Service (CAS), and Pathway Studio.
2021 Impact Factor: 3.650 (no longer indexed in SCIE as of 2022)
John D. Ash • Eric Pierce
Robert E. Anderson
Catherine Bowes Rickman
Joe G. Hollyfield • Christian Grimm
Editors

Retinal Degenerative
Diseases XIX
Mechanisms and Experimental
Therapy
Editors
John D. Ash Eric Pierce
Department of Ophthalmology Ocular Genomics Institute
University of Pittsburgh School Department of Ophthalmology
of Medicine Massachusetts Eye and Ear Infirmary
Pittsburgh, PA, USA Harvard Medical School
Boston, MA, USA
Robert E. Anderson
Health Sciences Center Catherine Bowes Rickman
University of Oklahoma Health Department of Ophthalmology
Sciences Center Duke Medical Center
Oklahoma City, OK, USA Durham, NC, USA

Joe G. Hollyfield Christian Grimm


Department of Ophthalmology Laboratory for Retinal Cell Biology
Cleveland Clinic Lerner College Department of Ophthalmology
of Medicine University Hospital Zurich
Cleveland, OH, USA University of Zurich
Schlieren, Switzerland

ISSN 0065-2598     ISSN 2214-8019 (electronic)


Advances in Experimental Medicine and Biology
ISBN 978-3-031-27680-4    ISBN 978-3-031-27681-1 (eBook)
https://doi.org/10.1007/978-3-031-27681-1

© The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature
Switzerland AG 2023
This work is subject to copyright. All rights are solely and exclusively licensed by the Publisher,
whether the whole or part of the material is concerned, specifically the rights of translation,
reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any
other physical way, and transmission or information storage and retrieval, electronic adaptation,
computer software, or by similar or dissimilar methodology now known or hereafter developed.
The use of general descriptive names, registered names, trademarks, service marks, etc. in this
publication does not imply, even in the absence of a specific statement, that such names are
exempt from the relevant protective laws and regulations and therefore free for general use.
The publisher, the authors, and the editors are safe to assume that the advice and information in
this book are believed to be true and accurate at the date of publication. Neither the publisher nor
the authors or the editors give a warranty, expressed or implied, with respect to the material
contained herein or for any errors or omissions that may have been made. The publisher remains
neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This Springer imprint is published by the registered company Springer Nature Switzerland AG
The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland
The editors are pleased dedicate this publication to the memory
of our long-time friend and colleague, Alan M. Laties. Except
for the most recent years, Alan attended each of these biennial
retinal degeneration meetings since they began in 1984. Early
on Alan recognized the importance of our attempt to provide a
continuing international platform for discussions and scientific
exchange to take place among investigators focused on retinal
degeneration research. Through his scientific leadership at the
Foundation Fighting Blindness (formerly the Retinitis
Pigmentosa Foundation), we received the first meeting grant to
partially cover some of the expenses of the RD meeting held in
San Francisco in 1988. The Foundation has provided
continuing support for each of the subsequent meetings in the
form of travel grant support for young investigators.
Born in Beverly, Massachusetts, the son of Russian immigrants,
he attended Harvard College (BA, 1954) and completed
medical school at Baylor College of Medicine (MD, 1959),
followed by a residency in ophthalmology in the Hospital of the
University of Pennsylvania (1961–63). A United States Public
Health Service Special Research Fellowship supported his
vi 

research training in the Institute of Neurological Sciences at


the University of Pennsylvania (1963–64). He joined the faculty
at the University of Pennsylvania in 1965 where he moved
through the academic ranks until retiring as Emeritus
Professor of Ophthalmology at the Perelman School of
Medicine in 2020. He held joint appointments in
Ophthalmology and Neurology where he was the Irene Heinz
Given and John LaPorte Given Research Professor and the
Harold G. Scheie Research Professor in Ophthalmology. He
served as neuro-ophthalmologist at the Hospital of the
University of Pennsylvania while pursuing basic research on
the autonomic innervation of the eye, eye growth, and
therapeutic approaches to eye diseases. He has published 140
original research papers, 30 review articles, and presented
numerous invited lectures at major university medical centers
around the world on a variety of topics critical to the treatment
of diseases of the eye. He was an inventor holding multiple
patents in the area of ophthalmology.
In the early 1970s, Alan was approached by the Retinitis
Pigmentosa Foundation to help them develop a scientific plan
to support targeted research that would lead to an
understanding of the causes of retinitis pigmentosa. At the time,
it was recognized that these diseases were inherited, but only in
a very limited way (autosomal dominant, recessive or
X-linked). At the time, no mutations causing RP had been
identified and the Human Genome Project would not be
initiated for another 20 years. Alan agreed and organized the
first Scientific Advisory Board for this Foundation and served
as Chairman. In this leadership role, Alan helped identify and
direct funding to the first laboratory focused on degenerative
retinal disease research, the Berman-Gund Laboratory at the
Massachusetts Eye and Ear Infirmary, Harvard University.
Research Centers focused on retinal degeneration would later
be expanded to many medical centers in North America,
England, and Europe. Alan recognized the importance and
need for animal models with these inherited retinal diseases
and directed funds from the Foundation to support the
development of the dog models with RP identified by Dr.
Gustavo Aguirre at the College of Veterinary Medicine. In the
early 1980s, Alan initiated a scientific plan for the Foundation
to identify the major genes responsible for RP. This led in 1989
to the discovery of a mutation in the rhodopsin gene
 vii

responsible for an autosomal dominant form of retinitis


pigmentosa. Discovery of mutations in other genes causing
retinitis pigmentosa quickly followed. With the discovery of
RP-65, a gene that causes a recessive form of RP, gene therapy
in a dog model with this recessive disorder could be quickly
initiated because of Dr. Laties’ early support from the
Foundation of these dog model lines. Dr. Laties’ early
leadership was hugely important to gene therapy clinical trials
and a number of other therapies related to these inherited
retinal diseases. To honor Dr. Laties, the Foundation Fighting
Blindness named their physicians’ and physician-scientists’
career development award the Alan Laties Career Development
Program and honored him with the inaugural Llura Liggett
Gund Lifetime Achievement Award.
Dr. Laties was a gifted scientist, outstanding leader, and
compassionate human who enriched the lives of his
contemporaries. He played a key role in nurturing and
expanding research in inherited retinal diseases. He is survived
by his wife Deena Gu, a distinguished artist, daughter Jane
Laties, sons Alex P. Laties and Nicholas P. Robinson, and a
brother, David.
Preface

The XIX International Symposium on Retinal Degeneration was held from


September 26 to October 2, 2021. The symposium was initially planned for
October of 2020 in Mendoza, Argentina. However, the global pandemic made
this meeting impossible. With the availability of vaccines, we decided in
March of 2021 that it would be possible to organize the meeting for late
September of 2021. From the beginning, we planned the meeting as an in-­
person meeting with the capability of switching to a hybrid or fully online
meeting depending on the state of the pandemic, and we moved the in-person
meeting to the United States to reduce travel complications for most attend-
ees. As the delta variant began to surge in the weeks leading up to the meet-
ing, we had to activate the hybrid meeting. The meeting platform we
established allowed both in-person and virtual platform talks as well as both
in-person and virtual attendance. The platform was organized so that all pre-
sentations were live and all participants were able to ask questions. All pre-
sentations, including posters, were recorded and made available 4 months
after the meeting. The in-person sessions were held in the Sonesta Nashville
Airport Hotel in Nashville, TN. Because of COVID concerns, the in-person
attendance was small (118 scientists) compared to previous meetings (~250
scientists), but the overall attendance increased to 344 attendees. The virtual
option was the main driver for the increase in attendance. The meeting pro-
gram included four outstanding keynote presentations from Michael Chiang,
Director of the National Eye Institute on Artificial intelligence for clinical
care and research; Douglas Wallace, National academy of Science member
and Professor at the University of Pennsylvania on Mitochondria and the eti-
ology of disease; David Gamm, Professor at the University of Wisconsin-­
Madison on Ultrathin micromolded 3D scaffolds for outer retina
reconstruction; Valeria Canto-Soler, Professor at the University of Colorado
on Human iPSC-derived 3D retinal tissue for stem cell-based therapies for
retinal degenerative diseases. Drs Chiang and Wallace presented via the vir-
tual platform, while Drs Gamm and Canto-Soler presented from the podium.
The program also included 41 platform talks, with 28 presented in person
from the podium and another 13 presented virtually. In addition, 143 posters
were presented as short talks on the virtual platform. Seventy-three of the
posters were also presented in person during two well-attended poster ses-
sions. New and important data were presented at the meeting, and we were
mentioned in a written article published on NPR, and several attendees were
interviewed by reporters from Science and other journals.

ix
x Preface

The RD2021 Travel award competition was highly successful at attracting


qualified applicants. We received a 35% increase in TA applications for a total
of 196. The applications were reviewed by a panel of 14 expert reviewers,
including 6 women, 8 men, and sceintists from a recognized underrepre-
sented minority (URM). Since funding from European sources is dedicated to
European early career scientists, we included three reviewers from Europe.
Many of the panel members have been prior travel awardees. Each applica-
tion was assigned four reviewers, and reviewers independently scored appli-
cations on a 1–9 scale. Based on scores, the applications are ranked and
slotted into funding sources based on funding agency criteria. We were able
to support full travel awards for 60 in-person early career scientists and
another 41 virtual early-career scientists. This is the largest pool of awardees
at an RD meeting. The awards were balanced between men and women. In
addition, we implemented a new diversity and inclusion policy and dedicated
a minimum of six awards to underrepresented minorities (URM). In the end,
we were able to fund 11 URMs to attend the RD meeting.
Although the pandemic made the RD2021 meeting more complex and
more challenging to organize, the RD2021 meeting was, by all accounts, a
terrific success.

Pittsburgh, PA, USA John D. Ash


Boston, MA, USA Eric Pierce
Oklahoma City, OK, USA Robert E. Anderson
Durham, NC, USA Catherine Bowes Rickman
Cleveland, OH, USA Joe G. Hollyfield
Schlieren, Switzerland Christian Grimm
Contents

Part I Age-related Macular Degeneration

High-Resolution Imaging Mass Spectrometry of Human


Donor Eye: Photoreceptors Cells and Basal Laminar
Deposit of Age-­Related Macular Degeneration������������������������������������   3
David M. G. Anderson, Ankita Kotnala, Jeffrey D. Messinger,
Nathan Heath Patterson, Jeffrey M. Spraggins, Christine A. Curcio,
Richard M. Caprioli, and Kevin L. Schey
The Noncanonical Role of Complement Factor H
in Retinal Pigment Epithelium (RPE) Cells and Implications
for Age-Related Macular Degeneration (AMD)������������������������������������   9
Angela Armento, David Adrian Merle, and Marius Ueffing
 acular Pigment Carotenoids and Bisretinoid A2E���������������������������� 15
M
Ranganathan Arunkumar and Paul S. Bernstein
Disturbed Matrix Metalloproteinases Activity in Age-Related
Macular Degeneration ���������������������������������������������������������������������������� 21
Beatriz Martins and Rosa Fernandes
Current Views on Chr10q26 Contribution to Age-Related
Macular Degeneration ���������������������������������������������������������������������������� 27
Navdeep Gogna, Lillian F. Hyde, Gayle B. Collin, Lisa Stone,
Jurgen K. Naggert, and Patsy M. Nishina
Untargeted Lipidomic Profiling of Aged Human Retina
With and Without Age-Related Macular Degeneration (AMD)���������� 37
Ankita Kotnala, David M. G. Anderson, Jeffrey D. Messinger,
Christine A. Curcio, and Kevin L. Schey
Decoding Race and Age-Related Macular Degeneration:
GPR 143 Activity Is the Key�������������������������������������������������������������������� 43
Dorothy Tung and Brian S. McKay
 eroxisome Proliferator-Activated Receptor Gamma
P
Coactivator-­1Alpha (PGC-1α): A Transcriptional Regulator at
the Interface of Aging and Age-Related Macular Degeneration? ������ 49
Freya M. Mowat

xi
xii Contents

Regulation of ABCA1 by miR-33 and miR-34a


in the Aging Eye �������������������������������������������������������������������������������������� 55
Florian Peters and Christian Grimm
 he Role of Gene Expression Regulation on Genetic Risk
T
of Age-­Related Macular Degeneration�������������������������������������������������� 61
Rinki Ratnapriya
Elastin Layer in Bruch’s Membrane as a Target
for Immunization or Tolerization to Modulate Pathology
in the Mouse Model of Smoke-Induced Ocular Injury������������������������ 67
Bärbel Rohrer, Nathaniel Parsons, Balasubramaniam Annamalai,
Crystal Nicholson, Elisabeth Obert, Bryan Jones,
and Andrew D. Dick
Repurposing Drugs for Treatment of Age-Related
Macular Degeneration ���������������������������������������������������������������������������� 73
Sarah G. Francisco and Sheldon Rowan

Part II Extracellular Vesicles

Extracellular Vesicle RNA Contents as Biomarkers


for Ocular Diseases���������������������������������������������������������������������������������� 81
Heran Getachew and Eric Pierce
Proteomics of Retinal Extracellular Vesicles: A Review
into an Unexplored Mechanism in Retinal Health
and AMD Pathogenesis���������������������������������������������������������������������������� 87
Adrian V. Cioanca, Riccardo Natoli, and Yvette Wooff

Part III Gene Editing

Prime Editing Strategy to Install the PRPH2


c.828+1G>A Mutation ���������������������������������������������������������������������������� 97
Salvatore Marco Caruso, Yi-Ting Tsai, Bruna Lopes da Costa,
Masha Kolesnikova, Laura A. Jenny, Stephen H. Tsang,
and Peter M. J. Quinn
Analysis of CRB1 Pathogenic Variants Correctable
with CRISPR Base and Prime Editing�������������������������������������������������� 103
Bruna Lopes da Costa, Laura A. Jenny, Irene H. Maumenee,
Stephen H. Tsang, and Peter M. J. Quinn
Generation of an Avian Myeloblastosis Virus (AMV)
Reverse Transcriptase Prime Editor������������������������������������������������������ 109
Yi-Ting Tsai, Bruna Lopes da Costa, Salvatore Marco Caruso,
Nicolas D. Nolan, Sarah R. Levi, Stephen H. Tsang,
and Peter M. J. Quinn
Contents xiii

Part IV Gene Therapy

Preexisting Neutralizing Antibodies against Different


Adeno-Associated Virus Serotypes in Humans
and Large Animal Models for Gene Therapy���������������������������������������� 117
Divya Ail and Deniz Dalkara
Optimization of Capillary-Based Western Blotting
for MYO7A ���������������������������������������������������������������������������������������������� 125
Kaitlyn R. Calabro, Sanford L. Boye, and Shannon E. Boye
AAV Serotypes and Their Suitability for Retinal
Gene Therapy ������������������������������������������������������������������������������������������ 131
Lynn J. A. Ebner and Christian Grimm
Gene Augmentation for Autosomal Dominant CRX-Associated
Retinopathies�������������������������������������������������������������������������������������������� 135
Chi Sun and Shiming Chen
 xnip Gene Therapy of Retinitis Pigmentosa Improves
T
Cone Health���������������������������������������������������������������������������������������������� 143
Yunlu Xue

Part V Human Retinal Degeneration

Factors Affecting Readthrough of Natural Versus


Premature Termination Codons ������������������������������������������������������������ 149
Avigail Beryozkin, Kerstin Nagel-Wolfum, Eyal Banin,
and Dror Sharon
Integrating Computational Approaches to Predict
the Effect of Genetic Variants on Protein Stability
in Retinal Degenerative Disease�������������������������������������������������������������� 157
Michelle Grunin, Ellen Palmer, Sarah de Jong, Bowen Jin,
David Rinker, Christopher Moth, John A. Capra,
Jonathan L. Haines, William S. Bush, and Anneke I. den Hollander
 etwork Biology and Medicine to Rescue: Applications
N
for Retinal Disease Mechanisms and Therapy�������������������������������������� 165
Anupam K. Mondal and Anand Swaroop
Non-syndromic Retinal Degeneration Caused by Pathogenic
Variants in Joubert Syndrome Genes���������������������������������������������������� 173
Riccardo Sangermano, Egle Galdikaité-Braziené,
and Kinga M. Bujakowska
Exonic Variants that Affect Splicing – An Opportunity
for “Hidden” Mutations Causing Inherited Retinal Diseases�������������� 183
Yogapriya Sundaresan, Eyal Banin, and Dror Sharon
 nhanced S-cone Syndrome, a Mini-review������������������������������������������ 189
E
Yiyi Wang, Jessica Wong, Jacque L. Duncan, Austin Roorda,
and William S. Tuten
xiv Contents

Part VI Inflammation

 he Role of Microglia in Inherited Retinal Diseases���������������������������� 197


T
Asha Kumari and Shyamanga Borooah
CD68: Potential Contributor to Inflammation and RPE
Cell Dystrophy������������������������������������������������������������������������������������������ 207
Mayur Choudhary and Goldis Malek
 ene Expression of Clusterin, Tissue Inhibitor
G
of Metalloproteinase-1, and Their Receptors in Retinal
Pigment Epithelial Cells and Müller Glial Cells Is
Modulated by Inflammatory Stresses���������������������������������������������������� 215
Mengmei Zheng, Eun-Jin Lee, Shinwu Jeong,
and Cheryl Mae Craft

Part VII Mechanisms of Degeneration

 xonal Transport Defects in Retinal Ganglion Cell Diseases�������������� 223


A
Iskalen Cansu Topcu Okan, Fatma Ozdemir, and Cavit Agca
 onnexins Biology in the Pathophysiology of Retinal Diseases���������� 229
C
Alejandro Ponce-Mora, Andrea Yuste, Giuliana Perini-Villanueva,
María Miranda, and Eloy Bejarano
 ole of Nuclear NAD+ in Retinal Homeostasis�������������������������������������� 235
R
Emily E. Brown, Michael J. Scandura, and Eric Pierce
Retinal Pigmented Epithelium-­Derived Ectopic Norrin Does
Not Promote Intraretinal Angiogenesis in Transgenic Mice���������������� 241
Andrea E. Dillinger and Ernst R. Tamm
Caveolin-1 in Müller Glia Exists as Heat-Resistant, High
Molecular Weight Complexes ���������������������������������������������������������������� 249
Eric N. Enyong, Jami Gurley, Virginie Sjoelung,
and Michael H. Elliott
 ole of VLC-PUFAs in Retinal and Macular Degeneration���������������� 257
R
Aruna Gorusupudi, Uzoamaka Nwagbo, and Paul S. Bernstein
Ocular Amyloid, Condensates, and Aggregates – Higher-Order
Protein Assemblies Participate in Both Retinal Degeneration
and Function�������������������������������������������������������������������������������������������� 263
Michael H. Hayes, DaNae R. Woodard, and John D. Hulleman
 hotoreceptor Ion Channels in Signaling and Disease������������������������ 269
P
Shivangi M. Inamdar, Colten K. Lankford, and Sheila A. Baker
The Role of Peripherin-2/ROM1 Complexes in Photoreceptor
Outer Segment Disc Morphogenesis������������������������������������������������������ 277
Tylor R. Lewis, Muayyad R. Al-Ubaidi, Muna I. Naash,
and Vadim Y. Arshavsky
Contents xv

Human Mutations in Arl3, a Small GTPase Involved


in Lipidated Cargo Delivery to the Cilia, Cause
Retinal Dystrophy������������������������������������������������������������������������������������ 283
Amanda M. Travis and Jillian N. Pearring
Genotype–Phenotype Association in ABCA4-Associated
Retinopathy���������������������������������������������������������������������������������������������� 289
Maximilian Pfau, Wadih M. Zein, Laryssa A. Huryn,
Catherine A. Cukras, Brett G. Jeffrey, Robert B. Hufnagel,
and Brian P. Brooks
Retinal Pathoconnectomics: A Window into
Neurodegeneration���������������������������������������������������������������������������������� 297
Rebecca L. Pfeiffer and Bryan W. Jones
The Role of Ceramide in Inherited Retinal
Disease Pathology������������������������������������������������������������������������������������ 303
Xinye Qian, Tanmay Srinivasan, Jessica He, and Rui Chen
 xtracellular Matrix: The Unexplored Aspects
E
of Retinal Pathologies and Regeneration���������������������������������������������� 309
Dmitri Serjanov and David R. Hyde
Role of TFEB in Diseases Associated with
Lysosomal Dysfunction���������������������������������������������������������������������������� 319
Hsuan-Yeh Pan and Mallika Valapala
Retinoic Acid Receptor-Related Orphan Receptors
(RORs) in Eye Development and Disease���������������������������������������������� 327
Felix Yemanyi, Kiran Bora, Alexandra K. Blomfield,
and Jing Chen

Part VIII Mechanisms of Degeneration – Animal Models

A Novel Mouse Model for Late-­Onset Retinal Degeneration


(L-ORD) Develops RPE Abnormalities Due
to the Loss of C1qtnf5/Ctrp5�������������������������������������������������������������������� 335
Shyamanga Borooah, Anil Chekuri, Shikha Pachauri,
Bhubananda Sahu, Marina Vorochikhina, John J. Suk,
Dirk-­Uwe Bartsch, Venkata R. M. Chavali, Monica M. Jablonski,
and Radha Ayyagari
 omparison of Mouse Models of Autosomal Dominant Retinitis
C
Pigmentosa Due to the P23H Mutation of Rhodopsin�������������������������� 341
Shannon R. Barwick and Sylvia B. Smith
Compensatory Cone-Mediated Mechanisms in Inherited
Retinal Degeneration Mouse Models: A Functional
and Gene Expression Analysis���������������������������������������������������������������� 347
Alicia A. Brunet, David M. Hunt, Carla Mellough,
Alan R. Harvey, and Livia S. Carvalho
xvi Contents

Inhibition of Ryanodine Receptor 1 Reduces Endoplasmic


Reticulum (ER) Stress and Promotes ER Protein
Degradation in Cyclic Nucleotide-Gated
Channel Deficiency���������������������������������������������������������������������������������� 353
Fan Yang, Hongwei Ma, Rekha Garg, Alfred Lewin,
and Xi-Qin Ding
 ouse Choroid Proteome Revisited: Focus on Aging�������������������������� 359
M
Donita Garland, James Harnly, and Radha Ayyagari
Morphological and Functional Comparison
of Mice Models for Retinitis Pigmentosa ���������������������������������������������� 365
Prakadeeswari Gopalakrishnan, Avigail Beryozkin,
Eyal Banin, and Dror Sharon
 urrent Advancements in Mouse Models of Retinal Disease�������������� 371
C
T. J. Hollingsworth, Xiangdi Wang, Raven N. Simpson,
William A. White, Robert W. Williams,
and Monica M. Jablonski
Single-Cell Transcriptomic Profiling of Müller
Glia in the rd10 Retina���������������������������������������������������������������������������� 377
Duygu Sigurdsson and Christian Grimm

Methods for In Vivo Characterization of Proteostasis
in the Mouse Retina �������������������������������������������������������������������������������� 383
Yixiao Wang and Ekaterina S. Lobanova
Absence of PRCD Leads to Dysregulation in Lipid
Homeostasis Resulting in Disorganization
of Photoreceptor Outer Segment Structure������������������������������������������ 389
Sree I. Motipally and Saravanan Kolandaivelu

Expansion Microscopy of Mouse Photoreceptor Cilia ������������������������ 395
Abigail R. Moyel, Michael A. Robichaux, and Theodore Wensel
Rod Photoreceptor-Specific Ablation of Metformin Target,
AMPK, in a Preclinical Model of Autosomal
Recessive Retinitis Pigmentosa �������������������������������������������������������������� 403
Nicholas D. Nolan, Laura A. Jenny, Stephen H. Tsang,
and Xuan Cui
TLR2 Is Highly Overexpressed in Retinal Myeloid
Cells in the rd10 Mouse Model of Retinitis Pigmentosa ���������������������� 409
Alonso Sánchez-Cruz, Enrique J. de la Rosa,
and Catalina Hernández-Sánchez
Environmental Light Has an Essential Effect
on the Disease Expression in a Dominant RPE65 Mutation���������������� 415
Wenjing Wu, Yusuke Takahashi, Xiang Ma, Gennadiy Moiseyev,
and Jian-Xing Ma
Contents xvii

Microglia Preserve Visual Function in a Mouse Model


of Retinitis Pigmentosa with Rhodopsin-P23H Mutant ���������������������� 421
Chen Yu and Daniel R. Saban

Part IX Mechanisms of Degeneration – Metabolism

Measuring the Release of Lactate from Wild-Type


and rd1 Mouse Retina������������������������������������������������������������������������������ 429
Yiyi Chen, Laimdota Zizmare, Christoph Trautwein,
and François Paquet-Durand
Aerobic Glycolysis in Photoreceptors Supports Energy
Demand in the Absence of Mitochondrial Coupling���������������������������� 435
Daniel T. Hass, Celia M. Bisbach, Martin Sadilek,
Ian R. Sweet, and James B. Hurley

Redox Status in Retinitis Pigmentosa���������������������������������������������������� 443
L. Olivares-González, S. Velasco, I. Campillo, J. M. Millán,
and R. Rodrigo
Perspectives on Retinal Dolichol Metabolism,
and Visual Deficits in Dolichol Metabolism-Associated
Inherited Disorders���������������������������������������������������������������������������������� 449
Sriganesh Ramachandra Rao, Steven J. Pittler,
and Steven J. Fliesler
Retinal Metabolic Profile on IMPG2 Deficiency Mice
with Subretinal Lesions �������������������������������������������������������������������������� 457
Rong Xu, Yekai Wang, Jianhai Du, and Ezequiel M. Salido

Part X Neuroprotection

Glutathione Coating of Liposomes Enhances the Delivery


of Hydrophilic Cargo to the Inner Nuclear Layer
in Retinal Cultures ���������������������������������������������������������������������������������� 467
Gustav Christensen and François Paquet-Durand
Modification of Müller Glial Cell Fate and Proliferation
with the Use of Small Molecules ������������������������������������������������������������ 473
Marcus J. Hooper
A Potential Neuroprotective Role for Pyruvate Kinase
2 in Retinal Degeneration������������������������������������������������������������������������ 479
Jiaming Zhou, Michel Rasmussen, and Per Ekström

Part XI Photoreceptors

Critical Role of VEGF as a Direct Regulator


of Photoreceptor Function���������������������������������������������������������������������� 487
Jianyan Hu, Meili Zhu, Dai Li, Qiang Wu, and Yun-Zheng Le
xviii Contents


Lysine Ubiquitylation Drives Rhodopsin Protein Turnover���������������� 493
Allen P. F. Chen, Leon Chea, Eun-Jin Lee,
and Jonathan H. Lin
 Silico Prediction of MYO1C-­Rhodopsin Interactions
In
and Its Significance in Protein Localization
and Visual Function �������������������������������������������������������������������������������� 499
Glenn P. Lobo, Rakesh Radhakrishnan, Matthias Leung,
Andrew Gruesen, Hans-­Joachim Knölker, Frederik J. van Kuijk,
and Sandra R. Montezuma
A Ciliary Branched Actin Network Drives
Photoreceptor Disc Morphogenesis�������������������������������������������������������� 507
William J. Spencer and Vadim Y. Arshavsky

Part XII RPE


Revisiting the Daily Timing of POS Phagocytosis�������������������������������� 515
Antonio E. Paniagua, Harjas S. Sabharwal, Kausalya Kethu,
Andrew W. Chang, and David S. Williams
Inhibition of Bacterial Peptidoglycan Cytopathy
by Retina Pigment Epithelial PGRP2 Amidase������������������������������������ 521
Marlyn P. Langford, Laura A. Perilloux-Lyons,
and A. Scott Kavanaugh
Understanding Ischemic Retinopathies: The Role
of Succinate and Its Receptor in Retinal
Pigment Epithelium �������������������������������������������������������������������������������� 527
Bilge Esin Ozturk

The Amphipathic Helix in Visual Cycle Proteins: A Review���������������� 533
Sheetal Uppal, Eugenia Poliakov, Susan Gentleman,
and T. Michael Redmond

The Retinal Pigment Epithelium: Cells That Know the Beat!������������ 539
Elora M. Vanoni and Emeline F. Nandrot

Part XIII Stem Cell Models and Therapies

Retinal Organoids: A Human Model System


for Development, Diseases, and Therapies�������������������������������������������� 549
Sangeetha Kandoi and Deepak A. Lamba

Modeling Retinitis Pigmentosa with Patient-Derived iPSCs �������������� 555
Yeh Chwan Leong and Jane C. Sowden

Primary Retinal Cell Cultures as a Model to Study
Retina Biology������������������������������������������������������������������������������������������ 565
Germán A. Michelis, Luis E. Politi, and S. Patricia Becerra
Contents xix

Generation of CRB1 RP Patient-­Derived iPSCs


and a CRISPR/Cas9-­Mediated Homology-Directed
Repair Strategy for the CRB1 c.2480G>T Mutation���������������������������� 571
Bruna Lopes da Costa, Yao Li, Sarah R. Levi, Stephen H. Tsang,
and Peter M. J. Quinn
Inducing Neural Regeneration from Glia Using Proneural
bHLH Transcription Factors������������������������������������������������������������������ 577
Levi Todd

Index�������������������������������������������������������������������������������������������������������� 583
Part I
Age-related Macular Degeneration
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