Article
Ophthalmology
Wei Liu, Ruru Guo, Huijie Hao, Jian Ji
Summary: A novel heterozygous nonsense mutation of RHO gene was identified in a Chinese family with retinitis pigmentosa through targeted region sequencing. Bioinformatics analysis indicated that the mutation is pathogenic, expanding the spectrum of RHO gene mutations and enriching the phenotype-genotype correlation of retinitis pigmentosa.
Article
Neurosciences
Chulbul M. Ahmeda, Michael T. Massengill, Cristhian J. Ildefonso, Archana Jalligampala, Ping Zhu, Hung Li, Anil P. Patel, Maureen A. McCall, Alfred S. Lewin
Summary: This study found that AAV-RHO820-shRNA820 can slow the loss of photoreceptor cells and preserve retinal function in P23H RHO transgenic mice. Moreover, the untreated contralateral eyes also showed the same protective effect. This suggests that RNA replacement therapy may provide clinical benefit to both eyes of adRP patients.
Article
Medicine, General & Internal
Yuanzheng Lan, Yuhong Chen, Yunsheng Qiao, Qingdan Xu, Ruyi Zhai, Xinghuai Sun, Jihong Wu, Xueli Chen
Summary: This study aimed to identify the genetic cause of autosomal dominant retinitis pigmentosa (adRP) in a Chinese family and investigate the molecular mechanisms of incomplete penetrance. Through whole-genome sequencing and RNA-seq analysis, a novel large deletion of a gene was identified in mutation carriers, leading to significant differential gene expression compared to healthy controls.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Shih-Fang Wu, Chih-Yao Lin, Rong-Kung Tsai, Yao-Tseng Wen, Feng-Huei Lin, Chia-Yu Chang, Ching- Shen, Shinn-Zong Lin, Horng-Jyh Harn, Tzyy-Wen Chiou, Chin-San Liu, Yan-Ting Chen, Hong-Lin Su
Summary: Research found that mitochondrial transplantation can moderately attenuate the degeneration of retinal layers in RCS rats. This result was confirmed through histological examination and OCT measurement of retina thickness. VEP analysis showed that the transmission time of electrical signals after mitochondrial transplantation was similar to the normal value. The results suggest that mitochondrial transplantation can improve the degeneration of photoreceptors in RCS rats and have potential for clinical application.
Article
Medicine, General & Internal
Tao Zhang, Jingshan Bai, Xinyi Zhang, Xiaowei Zheng, Nan Lu, Zhongyin Liang, Ling Lin, Yongsong Chen
Summary: This study identified a novel heterozygous SNRNP200(c.C6088T) mutation that causes retinitis pigmentosa through a dominant-negative effect.
FRONTIERS IN MEDICINE
(2021)
Article
Cell & Tissue Engineering
Eric D. Jong, Sabiha Hacibekiroglu, Lily Guo, Evan Sawula, Biao Li, Chengjin Li, Margaret T. Ho, Molly S. Shoichet, Valerie A. Wallace, Andras Nagy
Summary: A combined cell and gene therapy was developed for the treatment of retinitis pigmentosa (RP). Human embryonic stem cells (hESCs) were genetically engineered to differentiate into retinal pigment epithelium (hRPE) cells, which were used to protect and preserve photoreceptor cells in mouse models. This study reveals the potential of this therapy for RP treatment and the possibility of using hRPE cells for long-term delivery of therapeutic biologics.
STEM CELL RESEARCH & THERAPY
(2023)
Review
Neurosciences
Fangyuan Zhen, Tongdan Zou, Ting Wang, Yongwei Zhou, Shuqian Dong, Houbin Zhang
Summary: Rhodopsin is a light-sensitive receptor that initiates the phototransduction cascade. Mutations in the rhodopsin-encoding gene are the leading cause of retinitis pigmentosa. The high allelic heterogeneity suggests complex pathogenic mechanisms related to protein misfolding and dysfunction.
FRONTIERS IN NEUROSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Yogita Kanan, Sean F. Hackett, Henry T. Hsueh, Mahmood Khan, Laura M. Ensign, Peter A. Campochiaro
Summary: Retinitis pigmentosa (RP) is a genetic disorder that causes rod photoreceptor degeneration and subsequent cone photoreceptor degeneration. Reduced oxygen consumption from the loss of rods leads to retinal hyperoxia and oxidative stress, resulting in cone cell death and degeneration. However, reducing inspired oxygen levels can reduce retinal hyperoxia, preserve cone structure and function, and decrease oxidative damage in animal models of RP.
FREE RADICAL BIOLOGY AND MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Yang Liu, Yafang Wang, Yushu Xiao, Xiaomeng Li, Shang Ruan, Xueting Luo, Xiaoling Wan, Fenghua Wang, Xiaodong Sun
Summary: By establishing a CNGA1 knockout mouse model, researchers observed progressive retinal thinning and functional deficits as typical phenotypes for RP, along with degeneration in rods and cones, microglial activation, and oxidative stress damage. RNA-sequencing analysis indicated down-regulated synaptic transmission and phototransduction as early triggers for photoreceptor degeneration. The study contributes to understanding the mechanisms of photoreceptor death during RP progression and provides a novel model for potential therapeutic development.
Article
Biochemistry & Molecular Biology
Natalia Martinez-Gil, Oksana Kutsyr, Agustina Noailles, Laura Fernandez-Sanchez, Lorena Vidal, Xavier Sanchez-Saez, Carla Sanchez-Castillo, Pedro Lax, Nicolas Cuenca, Antonio G. Garcia, Victoria Maneu
Summary: P2X7R and P2X4R play important roles in retinal diseases and their expression increases during disease progression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Medicine, Research & Experimental
Wei Du, Jiarui Li, Xin Tang, Wenzhen Yu, Mingwei Zhao
Summary: In this study, a CRISPR/SaCas9-mediated gene reduction system was developed to inactivate Rho gene mutation and replace normal rhodopsin in a specific mouse model, leading to improved retinal function. These findings suggest that CRISPR/SaCas9-based reduction and replacement gene therapy could potentially offer therapeutic benefits for Rho mutant ADRP.
EXPERIMENTAL BIOLOGY AND MEDICINE
(2023)
Article
Anatomy & Morphology
Sohair A. Eltony, Heba S. Mohaseb, Amel A. Ahmed, Manal M. Sayed
Summary: This study aimed to investigate the effect of metformin on the retina of the ENU-induced rat model of RP. The results showed that metformin could reduce retinal degeneration and improve the morphology of glia and blood capillaries. This suggests that metformin has a neuroprotective effect on the retina.
Review
Biochemistry & Molecular Biology
Davide Allegrini, Raffaele Raimondi, Alfredo Borgia, Tania Sorrentino, Giovanni Montesano, Panos Tsoutsanis, Giuseppe Cancian, Yash Verma, Francesco Paolo De Rosa, Mario R. Romano
Summary: Recent evidence suggests that curcumin may be effective in treating retinal diseases by modulating gene transcription, reducing cell apoptosis, and improving vascular function. However, its limited bioavailability has hindered its use.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Ophthalmology
Yang Liu, Xin Wang, Ruowen Gong, Gezhi Xu, Min Zhu
Summary: Overexpression of WT RHO and its mutants leads to energy failure and cell death, with distinct impacts on the two energy metabolic pathways.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Ivona Bucan, Mirjana Bjelos, Irena Markovic, Diana Bucan
Summary: This article presents a rare case of a proven mutation in the RP1 gene in a kidney transplant patient. The patient showed signs of retinitis pigmentosa during an eye examination, and genetic testing confirmed a mutation in the RP1 gene. It is unclear why this gene mutation is specifically associated with retinal function and not with hypertension and renal disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Artur V. Cideciyan, Samuel G. Jacobson, Allen C. Ho, Alexandra V. Garafalo, Alejandro J. Roman, Alexander Sumaroka, Arun K. Krishnan, Malgorzata Swider, Michael R. Schwartz, Aniz Girach
Summary: Treatment of Leber congenital amaurosis due to CEP290 ciliopathy using antisense oligonucleotide (AON) sepofarsen shows significant efficacy, with sustained efficacy observed at 15 months despite a reduction from peak response. The efficacy kinetics can be explained by the balance of AON-driven new CEP290 protein synthesis and the slow natural rate of CEP290 protein degradation in human fovea cone photoreceptors.
Article
Ophthalmology
Alireza Badiei, William A. Beltran, Gustavo D. Aguirre
Summary: This study compared the expression levels of genes and proteins involved in retinal degeneration in normal dogs and canine models of inherited retinal degeneration. The results showed increased levels of H2S and NO in affected retinas, making cells vulnerable to oxidative damage and apoptosis.
EXPERIMENTAL EYE RESEARCH
(2022)
Article
Veterinary Sciences
Ana Ripolles-Garcia, Dolores M. Holle, Julie A. Cohen, William A. Beltran, Gustavo D. Aguirre
Summary: This study utilized advanced retinal imaging techniques to visualize the in vivo structural characteristics of multifocal and geographic retinal dysplasia in two dogs. The findings revealed morphological patterns of the lesions, vascular anomalies, increased autofluorescence, and photoreceptor loss associated with the dysplasia, demonstrating the potential of OCTA in identifying microvascular abnormalities in canine retinas.
VETERINARY OPHTHALMOLOGY
(2022)
Review
Veterinary Sciences
Gustavo D. Aguirre, Kevin R. Kazacos
Summary: The term retinopathy is used to categorize various retinal abnormalities that are either acquired or suspected/proposed to be inherited, some of which exhibit characteristic tapetal lesions with depigmentation suggestive of retinal atrophy. It is discussed whether ocular larva migrans leading to canine DUSN may be responsible for certain retinal findings grouped under retinopathy with similar fundus lesions.
VETERINARY OPHTHALMOLOGY
(2022)
Article
Veterinary Sciences
Yu Sato, Alexa Gray, Kei Takahashi, Valerie Dufour, Gerard Lutty, Keiko Miyadera, Gustavo Aguirre
Summary: This study described a case of monocular retinopathy of prematurity (ROP)-like vasculopathy in a dog without oxygen supplementation. The findings suggest that abnormal vascular patterns seen in ROP in premature infants can also occur in canines without oxygen administration.
VETERINARY OPHTHALMOLOGY
(2022)
Article
Veterinary Sciences
Alexa P. Gray, Yu Sato, Keiko Miyadera, Gustavo D. Aguirre
Summary: The purpose of this study was to describe the in vivo microanatomy of typical and atypical chorioretinal and juxtapapillary colobomas in dogs. Advanced retinal imaging techniques, including OCT, were used to characterize features observed in these colobomas and detect structural changes not visible by ophthalmoscopy alone. This study highlights the importance of using advanced imaging tools to better understand microanatomical changes in the living eye.
VETERINARY OPHTHALMOLOGY
(2022)
Article
Multidisciplinary Sciences
Keiko Miyadera, Evelyn Santana, Karolina Roszak, Sommer Iffrig, Meike Visel, Simone Iwabe, Ryan F. Boyd, Joshua T. Bartoe, Yu Sato, Alexa Gray, Ana Ripolles-Garcia, Valerie L. Dufour, Leah C. Byrne, John G. Flannery, William A. Beltran, Gustavo D. Aguirre
Summary: This study demonstrates the safe and effective targeting of ON-bipolar cells (ON-BCs) through AAV gene therapy in a naturally occurring canine model of congenital stationary night blindness (CSNB). By using AAV capsid variants with ON-BC tropism and ON-BC-specific modified GRM6 promoters, the researchers were able to successfully recover visual function and establish a translational platform for the treatment of CSNB.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Ophthalmology
Alejandro J. Roman, Artur V. Cideciyan, Vivian Wu, Abraham A. Mascio, Arun K. Krishnan, Alexandra V. Garafalo, Samuel G. Jacobson
Summary: This study developed a mobility task to quantify functional vision in patients with LCA. Combined with other measurements of rod and cone photoreceptor-mediated vision, dark-adapted functional vision can provide a more comprehensive understanding of the natural history and treatment effects in LCA patients.
Article
Medicine, Research & Experimental
Alfred S. S. Lewin, W. Clay Smith
Summary: Mutations in the RHO gene are a significant cause of autosomal-dominant retinitis pigmentosa. There are two clinical classes of patients - those with early onset and those with slowly progressive disease. Gene therapy can target the mutant gene at the DNA or RNA level, while other therapies aim to preserve photoreceptor viability.
COLD SPRING HARBOR PERSPECTIVES IN MEDICINE
(2022)
Article
Neurosciences
Artur Cideciyan, Samuel G. Jacobson, Alexander Sumaroka, Malgorzata Swider, Arun K. Krishnan, Rebecca Sheplock, Alexandra V. Garafalo, Karina E. Guziewicz, Gustavo D. Aguirre, William A. Beltran, Yoshitsugu Matsui, Mineo Kondo, Elise Heon
Summary: The only approved retinal gene therapy is for biallelic RPE65 mutations which cause a recessive retinopathy with a primary molecular defect located at the retinal pigment epithelium (RPE). For a distinct recessive RPE disease caused by biallelic BEST1 mutations, a pre-clinical proof-of-concept for gene therapy has been demonstrated in canine eyes. The current study was undertaken to consider potential outcome measures for a BEST1 clinical trial in patients demonstrating a classic autosomal recessive bestrophinopathy (ARB) phenotype.
Article
Neurosciences
Chulbul M. Ahmeda, Michael T. Massengill, Cristhian J. Ildefonso, Archana Jalligampala, Ping Zhu, Hung Li, Anil P. Patel, Maureen A. McCall, Alfred S. Lewin
Summary: This study found that AAV-RHO820-shRNA820 can slow the loss of photoreceptor cells and preserve retinal function in P23H RHO transgenic mice. Moreover, the untreated contralateral eyes also showed the same protective effect. This suggests that RNA replacement therapy may provide clinical benefit to both eyes of adRP patients.
Meeting Abstract
Ophthalmology
Stephen R. Russell, Arlene V. Drack, Artur V. Cideciyan, Samuel G. Jacobson, Bart P. Leroy, Caroline Van Cauwenbergh, Michael Schwartz, Aniz Girach
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2022)
Meeting Abstract
Ophthalmology
William A. Beltran, Artur V. Cideciyan, Ana Ripolles-Garcia, Valerie L. Dufour, Yu Sato, Alexa Gray, Malgorzata Swider, Sanford L. Boye, William W. Hauswirth, Samuel G. Jacobson, Gustavo D. Aguirre
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2022)