Featured
-
-
Article
| Open AccessLate gene therapy limits the restoration of retinal function in a mouse model of retinitis pigmentosa
Is there a critical period to deliver gene therapies in photoreceptor degeneration? Using a mouse model of retinitis pigmentosa, the authors show that once 70% of rods are lost, gene replacement fails to restore normal retinal output.
- Miranda L. Scalabrino
- , Mishek Thapa
- & Greg D. Field
-
Article
| Open AccessUncertainty-inspired open set learning for retinal anomaly identification
Failure to recognize samples from unseen classes is a major limitation of AI recognition and classification of retinal anomalies. Here, the authors present the Uncertainty-inspired Open Set learning model that categorises fundus images into pre-trained categories, and provides an uncertainty score that alerts the need for manual inspection when dealing with out-of-distribution images.
- Meng Wang
- , Tian Lin
- & Huazhu Fu
-
Article
| Open AccessmRNA trans-splicing dual AAV vectors for (epi)genome editing and gene therapy
Large genes require dual adeno-associated viral (AAV) vectors for in vivo delivery/expression, but current methods have limitations. Here the authors develop and functionally evaluate REVeRT, an efficient and flexible dual AAV vector technology based on reconstitution via mRNA trans-splicing.
- Lisa Maria Riedmayr
- , Klara Sonnie Hinrichsmeyer
- & Elvir Becirovic
-
Article
| Open AccessAAV-mediated base-editing therapy ameliorates the disease phenotypes in a mouse model of retinitis pigmentosa
Base editing technology has great potential in treating pathogenic single-nucleotide variations. Using a dual-AAV base editing system, Wu et al. restored visual functions in a mouse model of retinitis pigmentosa.
- Yidong Wu
- , Xiaoling Wan
- & Xueli Zhang
-
Article
| Open AccessImbalanced unfolded protein response signaling contributes to 1-deoxysphingolipid retinal toxicity
The accumulation of cytotoxic deoxysphingolipids causes retinopathies through unknown mechanisms. Here the authors use retinal organoids to show that photoreceptor toxicity is mediated by unfolded protein response signaling.
- Jessica D. Rosarda
- , Sarah Giles
- & Kevin T. Eade
-
Article
| Open AccessA visual opsin from jellyfish enables precise temporal control of G protein signalling
Jellyfish see light in a similar way that vertebrates smell odours. Here, Michiel van Wyk and Sonja Kleinlogel show how jellyfish has adapted this slow signal detection pathway to support sophisticated vision, and use a similar method to restore vision in blind mice.
- Michiel van Wyk
- & Sonja Kleinlogel
-
Article
| Open AccessThe inner junction protein CFAP20 functions in motile and non-motile cilia and is critical for vision
Motile and non-motile cilia have distinct functions and protein complexes associated with them. Here, the authors show the conserved protein CFAP20 is important for both motile and non-motile cilia and is distinct from other ciliopathy-associated domains or macromolecular complexes.
- Paul W. Chrystal
- , Nils J. Lambacher
- & Michel R. Leroux
-
Article
| Open AccessReducing Akt2 in retinal pigment epithelial cells causes a compensatory increase in Akt1 and attenuates diabetic retinopathy
Retinal pigment epithelium (RPE) plays an important role in diabetic retinopathy (DR) progression. Here, the authors show AKT1 and AKT2 are reciprocally regulated in the RPE of DR donor tissue and diabetic mice, reducing Akt2 in RPE causing a compensatory increase in Akt1 and attenuating DR.
- Haitao Liu
- , Nadezda A. Stepicheva
- & Debasish Sinha
-
Article
| Open AccessHigh-resolution genome topology of human retina uncovers super enhancer-promoter interactions at tissue-specific and multifactorial disease loci
The genome-wide high-resolution chromatin contact of the human retina identifies genetic control of cell-type specific gene expression pattern, missing heritability in retinopathies, and candidate genes/variants for diseases including AMD and glaucoma.
- Claire Marchal
- , Nivedita Singh
- & Anand Swaroop
-
Article
| Open AccessTargeting retinoic acid receptor alpha-corepressor interaction activates chaperone-mediated autophagy and protects against retinal degeneration
Gomez-Sintes et al. have developed small molecules that selectively activate chaperone-mediated autophagy by stabilizing the interaction between retinoic acid receptor alpha and its co-repressor N-CoR1. They demonstrate the protective effect of boosting chaperone-mediated autophagy against retinal degeneration.
- Raquel Gomez-Sintes
- , Qisheng Xin
- & Ana Maria Cuervo
-
Article
| Open AccessAutomatic detection of 39 fundus diseases and conditions in retinal photographs using deep neural networks
Systems for automatic detection of a single disease may miss other important conditions. Here, the authors show a deep learning platform can detect 39 common retinal diseases and conditions.
- Ling-Ping Cen
- , Jie Ji
- & Mingzhi Zhang
-
Article
| Open AccessA deep learning system for detecting diabetic retinopathy across the disease spectrum
As the leading cause of vision loss in working-age adults, diabetic retinopathy requires routinely retinal screening. Here the authors develop a deep learning system that can facilitate the screening by providing real-time image quality assessment, lesions detection, and grades across the disease spectrum.
- Ling Dai
- , Liang Wu
- & Weiping Jia
-
Article
| Open AccessAberrant TGF-β1 signaling activation by MAF underlies pathological lens growth in high myopia
High myopia is associated with lens changes, but the underlying mechanisms are unclear. Here, the authors show increased equatorial diameter of the lens in subjects affected by high myopia, and find that these changes are associated with an increase in crystallin expression driven by the transcription factor MAF and TGF-β1 signaling.
- Xiangjia Zhu
- , Yu Du
- & Yi Lu
-
Article
| Open AccessChain-like gold nanoparticle clusters for multimodal photoacoustic microscopy and optical coherence tomography enhanced molecular imaging
This manuscript presents ultrapure chain-like gold nanoparticle clusters with red shifted absorption and shows their potential for in vivo imaging in living rabbits. The nanoparticles demonstrate a 17-fold increase in photoacoustic microscopy signal and 176% increase in optical coherence tomography signal.
- Van Phuc Nguyen
- , Wei Qian
- & Yannis M. Paulus
-
Article
| Open AccessVascular progenitors generated from tankyrase inhibitor-regulated naïve diabetic human iPSC potentiate efficient revascularization of ischemic retina
hPSCs in culture acquire a more naïve pluripotent state upon tankyrase inhibition. Here, the authors show that tankyrase inhibitor-regulated naïve hiPSCs from diabetic donors generate more vascular progenitors and more efficient engraftment into mouse retina than conventional PSCs.
- Tea Soon Park
- , Ludovic Zimmerlin
- & Elias T. Zambidis
-
Article
| Open AccessSustained treatment of retinal vascular diseases with self-aggregating sunitinib microparticles
Neovascular age-related macular degeneration and diabetic retinopathy are currently treated with repeated intravitreous injections of VEGF neutralizing proteins. Here the authors develop a microparticle-loaded tyrosine kinase inhibitor therapy, which is effective for six months after a single injection in preclinical models.
- Hiroki Tsujinaka
- , Jie Fu
- & Peter A. Campochiaro
-
Article
| Open AccessIntravenous treatment of choroidal neovascularization by photo-targeted nanoparticles
Current treatments of wet age-related macular degeneration require repeated injections of active drugs into the vitreous. Here Wang et al. develop nanoparticles that when injected intravenously can be targeted to the eye by irradiation with blue light, allowing local and enhanced drug release in the back of the eye, and providing an alternative to current delivery strategies.
- Yanfei Wang
- , Chi-Hsiu Liu
- & Daniel S. Kohane
-
Article
| Open AccessNCK-dependent pericyte migration promotes pathological neovascularization in ischemic retinopathy
Pericytes are perivascular cells that regulate blood vessel formation and function. Here Dubrac et al. show that pericyte recruitment contributes to pathological neovascularisation in a mouse model of ischemic retinopathy, and that this depends on the regulation of PDGF-B signaling by NCK adaptor proteins.
- Alexandre Dubrac
- , Steffen E. Künzel
- & Anne Eichmann
-
Article
| Open AccessA novel small molecule chaperone of rod opsin and its potential therapy for retinal degeneration
Mutations that lead to misfolding of rhodopsin can cause retinitis pigmentosa. Here, the authors carry out a high throughput screen to identify a small molecule chaperone of rod opsin, and show that it protects mouse models of retinitis pigmentosa from retinal degeneration.
- Yuanyuan Chen
- , Yu Chen
- & Krzysztof Palczewski
-
Article
| Open AccessCCDC102B confers risk of low vision and blindness in high myopia
Myopic maculopathy is a complication of myopia that often progresses to blindness. Here, in a genome-wide association study, Hosoda et al. find that rs11873439 intronic to CCDC102B is associated with myopic maculopathy, but not with myopia, thus representing a risk factor independent of myopia.
- Yoshikatsu Hosoda
- , Munemitsu Yoshikawa
- & Kenji Yamashiro
-
Article
| Open AccessFoxp3+ Tregs are recruited to the retina to repair pathological angiogenesis
The local immune responses in the eye are attenuated to preserve sight. Surprisingly, Deliyanti et al. show that regulatory T cells (Tregs) take an active role in protecting the eye from neovascularization in oxygen-induced retinopathy, and that interventions that augment the retinal Treg numbers reduce neovascular retinopathy in mice.
- Devy Deliyanti
- , Dean M. Talia
- & Jennifer L. Wilkinson-Berka
-
Article
| Open AccessEndothelial adenosine A2a receptor-mediated glycolysis is essential for pathological retinal angiogenesis
Pathological angiogenesis in the retina is a major cause of blindness. Here the authors show that adenosine receptor A2A drives pathological angiogenesis in the oxygen-induced retinopathy mouse model by promoting glycolysis in endothelial cells via the ERK/Akt/HIF-1α pathway, thereby suggesting new therapeutic targets for disease treatment.
- Zhiping Liu
- , Siyuan Yan
- & Yuqing Huo
-
Article
| Open AccessGelsolin dysfunction causes photoreceptor loss in induced pluripotent cell and animal retinitis pigmentosa models
Mutations in the Retinitis Pigmentosa GTPase Regulator (RPGR) cause retinal dystrophy, but how this arises at a molecular level is unclear. Here, the authors show in induced pluripotent stem cells and mouse knockouts that RPGR mediates actin dynamics in photoreceptors via the actin-severing protein, gelsolin.
- Roly Megaw
- , Hashem Abu-Arafeh
- & Charles ffrench-Constant
-
Article
| Open AccessPlastic roles of pericytes in the blood–retinal barrier
Blood-retinal barrier (BRB) is composed of tightly connected endothelium and supporting pericytes and glia. Here, the authors show that pericytes are crucial for BRB buildup during retinal development and its maintenance in adult retinas in response to VEGF-A-induced endothelial sensitization by regulating the Tie2/FOXO1/Ang2 axis.
- Do Young Park
- , Junyeop Lee
- & Gou Young Koh
-
Article
| Open AccessNrl knockdown by AAV-delivered CRISPR/Cas9 prevents retinal degeneration in mice
Retinitis pigmentosa is mainly caused by mutations that initially affect survival of rod photoreceptors, leading to secondary loss of cones. Here the authors use gene editing to prevent rod degeneration, leading to survival of cones and improved vision in mice.
- Wenhan Yu
- , Suddhasil Mookherjee
- & Zhijian Wu
-
Article
| Open AccessGuanine nucleotide binding to the Bateman domain mediates the allosteric inhibition of eukaryotic IMP dehydrogenases
IMP dehydrogenase (IMPDH) plays essential roles in purine metabolism and cell proliferation. Here Buey et al. describe a guanine nucleotides regulated molecular mechanism for allosteric communication between the regulatory and catalytic domains of IMPDH.
- Rubén M. Buey
- , Rodrigo Ledesma-Amaro
- & José L. Revuelta
-
Article
| Open AccessAdiponectin receptor 1 conserves docosahexaenoic acid and promotes photoreceptor cell survival
Docosahexaenoic acid is a major and important retinal fatty acid that is recruited and retained in the photoreceptor membrane via an unknown mechanism. Here, Rice et al. show that adiponectin receptor 1 is a key molecular switch for docosahexaenoic acid membrane homeostasis and photoreceptor cell function.
- Dennis S. Rice
- , Jorgelina M. Calandria
- & Nicolas G. Bazan
-
Article
| Open AccessGene therapy restores vision in rd1 mice after removal of a confounding mutation in Gpr179
The rd1 mouse is the most widely used model to study retinal degeneration. Here, the authors identify a wide-spread mutation in these mice that may explain the failure of previous gene therapeutic approaches and show that long-lasting restoration of vision is possible in rd1 mice without this mutation.
- Koji M. Nishiguchi
- , Livia S. Carvalho
- & Robin R. Ali
-
Article |
Mutations in PNPLA6 are linked to photoreceptor degeneration and various forms of childhood blindness
Blindness due to retinal degeneration affects millions of people worldwide, but many disease-causing mutations remain unknown. Here the authors link mutations in the gene PNPLA6 with childhood blindness in seven families with retinal degeneration and show that the gene plays a role in photoreceptor survival in Drosophila.
- S. Kmoch
- , J. Majewski
- & R. K. Koenekoop