scholarly journals Pathways and disease-causing alterations in visual chromophore production for vertebrate vision

2020 ◽  
pp. jbc.REV120.014405 ◽  
Author(s):  
Philip D Kiser ◽  
Krzysztof Palczewski
Keyword(s):  
Retinal Dystrophy ◽  
Bright Light ◽  
Photoreceptor Cells ◽  
Age Related Macular Degeneration ◽  
Retinal Diseases ◽  
Visual Cycle ◽  
Light Conditions ◽  
Age Related ◽  
G Protein Coupled ◽  
Rod And Cone Photoreceptors

All that we view of the world begins with an ultrafast cis to trans photoisomerization of the retinylidene chromophore associated with the visual pigments of rod and cone photoreceptors. The continual responsiveness of these photoreceptors is then sustained by regeneration processes that convert the trans- retinoid back to an 11-cis configuration. Recent biochemical and electrophysiological analyses of the retinal G protein-coupled receptor (RGR) suggest that it could sustain the responsiveness of photoreceptor cells, particularly cones, even under bright light conditions. Thus, two mechanisms have evolved to accomplish the re-isomerization: one involving the well-studied retinoid isomerase (RPE65), and a second photoisomerase reaction mediated by the RGR. Impairments to the pathways that transform all- trans-retinal back to 11-cis-retinal are associated with mild to severe forms of retinal dystrophy. Moreover, with age there also is a decline in the rate of chromophore regeneration. Both pharmacological and genetic approaches are being used to bypass visual cycle defects and consequently mitigate blinding diseases.  Rapid progress in the use of genome editing also is paving the way for the treatment of disparate retinal diseases. In this review, we provide an update on visual cycle biochemistry and then discuss visual cycle-related diseases and emerging therapeutics for these disorders. There is hope that these advances will be helpful in treating more complex diseases of the eye, including age-related macular degeneration (AMD).

Gene editing prospects for treating inherited retinal diseases

2019 ◽  
Vol 57 (7) ◽  
pp. 437-444 ◽  
Author(s):  
Daniela Benati ◽  
Clarissa Patrizi ◽  
Alessandra Recchia
Keyword(s):  
Genome Editing ◽  
Genetic Disorder ◽  
Retinal Pigment ◽  
Treatment Options ◽  
Genetic Defect ◽  
Retinal Dystrophy ◽  
Retinal Pigment Epithelial Cells ◽  
Age Related Macular Degeneration ◽  
Retinal Diseases ◽  
Age Related

Retinal diseases (RD) include inherited retinal dystrophy (IRD), for example, retinitis pigmentosa and Leber’s congenital amaurosis, or multifactorial forms, for example, age-related macular degeneration (AMD). IRDs are clinically and genetically heterogeneous in nature. To date, more than 200 genes are known to cause IRDs, which perturb the development, function and survival of rod and cone photoreceptors or retinal pigment epithelial cells. Conversely, AMD, the most common cause of blindness in the developed world, is an acquired disease of the macula characterised by progressive visual impairment. To date, available therapeutic approaches for RD include nutritional supplements, neurotrophic factors, antiangiogenic drugs for wet AMD and gene augmentation/interference strategy for IRDs. However, these therapies do not aim at correcting the genetic defect and result in inefficient and expensive treatments. The genome editing technology based on clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein (Cas) and an RNA that guides the Cas protein to a predetermined region of the genome, represents an attractive strategy to tackle IRDs without available cure. Indeed, CRISPR/Cas system can permanently and precisely replace or remove genetic mutations causative of a disease, representing a molecular tool to cure a genetic disorder. In this review, we will introduce the mechanism of CRISPR/Cas system, presenting an updated panel of Cas variants and delivery systems, then we will focus on applications of CRISPR/Cas genome editing in the retina, and, as emerging treatment options, in patient-derived induced pluripotent stem cells followed by transplantation of retinal progenitor cells into the eye.

scholarly journals Kinins and Their Receptors as Potential Therapeutic Targets in Retinal Pathologies

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1913
Author(s):  
Rahmeh Othman ◽  
Gael Cagnone ◽  
Jean-Sébastien Joyal ◽  
Elvire Vaucher ◽  
Réjean Couture
Keyword(s):  
Renin Angiotensin System ◽  
Age Related Macular Degeneration ◽  
Retinal Diseases ◽  
Kinin System ◽  
Physiological Processes ◽  
Kinin Receptors ◽  
Age Related ◽  
Kallikrein Kinin System ◽  
Retinal Pathologies ◽  
G Protein Coupled

The kallikrein-kinin system (KKS) contributes to retinal inflammation and neovascularization, notably in diabetic retinopathy (DR) and neovascular age-related macular degeneration (AMD). Bradykinin type 1 (B1R) and type 2 (B2R) receptors are G-protein-coupled receptors that sense and mediate the effects of kinins. While B2R is constitutively expressed and regulates a plethora of physiological processes, B1R is almost undetectable under physiological conditions and contributes to pathological inflammation. Several KKS components (kininogens, tissue and plasma kallikreins, and kinin receptors) are overexpressed in human and animal models of retinal diseases, and their inhibition, particularly B1R, reduces inflammation and pathological neovascularization. In this review, we provide an overview of the KKS with emphasis on kinin receptors in the healthy retina and their detrimental roles in DR and AMD. We highlight the crosstalk between the KKS and the renin–angiotensin system (RAS), which is known to be detrimental in ocular pathologies. Targeting the KKS, particularly the B1R, is a promising therapy in retinal diseases, and B1R may represent an effector of the detrimental effects of RAS (Ang II-AT1R).

An Intraocular Camera for Retinal Prostheses

2007 ◽  
Author(s):  
Patrick J. Nasiatka ◽  
Michelle C. Hauer ◽  
Noelle R. B. Stiles ◽  
Jaw-Chyng Lue ◽  
Satsuki Takahashi ◽  
...  
Keyword(s):  
Photoreceptor Cells ◽  
Head Movements ◽  
Age Related Macular Degeneration ◽  
Depth Of Field ◽  
Retinal Diseases ◽  
Retinal Neurons ◽  
Retinal Prostheses ◽  
Retinal Implants ◽  
Age Related ◽  
Functional Vision

Blindness due to degenerative retinal diseases such as Retinitis Pigmentosa (RP) and Age-Related Macular Degeneration (AMD) afflict millions of people worldwide. Recent advances in retinal implants that bypass damaged photoreceptor cells and electrically stimulate the remaining healthy retinal neurons show promise for restoring functional vision to the blind [1]. Current intraocular retinal prostheses driven by an external camera mounted on the subject’s head require slow and unnatural head movements. To allow for normal foveation and expanded depth of field, a novel intraocular camera (IOC) has been designed to work in conjunction with an epiretinal microstimulator array, as shown schematically in Fig. 1.

scholarly journals Development of a Fundus Image-Based Deep Learning Diagnostic Tool for Various Retinal Diseases

2021 ◽  
Vol 11 (5) ◽  
pp. 321
Author(s):  
Kyoung Min Kim ◽  
Tae-Young Heo ◽  
Aesul Kim ◽  
Joohee Kim ◽  
Kyu Jin Han ◽  
...  
Keyword(s):  
Network Models ◽  
Retinal Disease ◽  
Age Related Macular Degeneration ◽  
Diagnostic Tools ◽  
Retinal Images ◽  
Dense Layer ◽  
Retinal Diseases ◽  
Fundus Image ◽  
Neural Network Models ◽  
Age Related

Artificial intelligence (AI)-based diagnostic tools have been accepted in ophthalmology. The use of retinal images, such as fundus photographs, is a promising approach for the development of AI-based diagnostic platforms. Retinal pathologies usually occur in a broad spectrum of eye diseases, including neovascular or dry age-related macular degeneration, epiretinal membrane, rhegmatogenous retinal detachment, retinitis pigmentosa, macular hole, retinal vein occlusions, and diabetic retinopathy. Here, we report a fundus image-based AI model for differential diagnosis of retinal diseases. We classified retinal images with three convolutional neural network models: ResNet50, VGG19, and Inception v3. Furthermore, the performance of several dense (fully connected) layers was compared. The prediction accuracy for diagnosis of nine classes of eight retinal diseases and normal control was 87.42% in the ResNet50 model, which added a dense layer with 128 nodes. Furthermore, our AI tool augments ophthalmologist’s performance in the diagnosis of retinal disease. These results suggested that the fundus image-based AI tool is applicable for the medical diagnosis process of retinal diseases.

scholarly journals Drusen in patient-derived hiPSC-RPE models of macular dystrophies

2017 ◽  
Vol 114 (39) ◽  
pp. E8214-E8223 ◽  
Author(s):  
Chad A. Galloway ◽  
Sonal Dalvi ◽  
Sandy S. C. Hung ◽  
Leslie A. MacDonald ◽  
Lisa R. Latchney ◽  
...  
Keyword(s):  
Vision Loss ◽  
Retinal Pigment ◽  
Retinal Dystrophy ◽  
Age Related Macular Degeneration ◽  
In Vivo Studies ◽  
Specific Cell ◽  
Rpe Cells ◽  
Age Related ◽  
Pathway Gene ◽  
Human Pathology

Age-related macular degeneration (AMD) and related macular dystrophies (MDs) are a major cause of vision loss. However, the mechanisms underlying their progression remain ill-defined. This is partly due to the lack of disease models recapitulating the human pathology. Furthermore, in vivo studies have yielded limited understanding of the role of specific cell types in the eye vs. systemic influences (e.g., serum) on the disease pathology. Here, we use human induced pluripotent stem cell-retinal pigment epithelium (hiPSC-RPE) derived from patients with three dominant MDs, Sorsby’s fundus dystrophy (SFD), Doyne honeycomb retinal dystrophy/malattia Leventinese (DHRD), and autosomal dominant radial drusen (ADRD), and demonstrate that dysfunction of RPE cells alone is sufficient for the initiation of sub-RPE lipoproteinaceous deposit (drusen) formation and extracellular matrix (ECM) alteration in these diseases. Consistent with clinical studies, sub-RPE basal deposits were present beneath both control (unaffected) and patient hiPSC-RPE cells. Importantly basal deposits in patient hiPSC-RPE cultures were more abundant and displayed a lipid- and protein-rich “drusen-like” composition. Furthermore, increased accumulation of COL4 was observed in ECM isolated from control vs. patient hiPSC-RPE cultures. Interestingly, RPE-specific up-regulation in the expression of several complement genes was also seen in patient hiPSC-RPE cultures of all three MDs (SFD, DHRD, and ADRD). Finally, although serum exposure was not necessary for drusen formation, COL4 accumulation in ECM, and complement pathway gene alteration, it impacted the composition of drusen-like deposits in patient hiPSC-RPE cultures. Together, the drusen model(s) of MDs described here provide fundamental insights into the unique biology of maculopathies affecting the RPE–ECM interface.

scholarly journals Review of Subthreshold Diode Micropulse Laser Treatment for Retinal Diseases

2018 ◽  
Vol 1 (1) ◽  
pp. 62-70
Author(s):  
Juhn AT ◽  
Shyu AP ◽  
Benjamin J ◽  
Zhang Y
Keyword(s):  
Diabetic Retinopathy ◽  
Treatment Modality ◽  
Branch Retinal Vein Occlusion ◽  
Age Related Macular Degeneration ◽  
Clinical Settings ◽  
Retinal Diseases ◽  
Micropulse Laser ◽  
Vein Occlusion ◽  
Age Related ◽  
New Treatment

Subthreshold Diode Micropulse (SDM) laser is a relatively new treatment modality that confers very little to no anatomical risk to the retina. However, its efficacy is still being studied, and the scenario where SDM is most useful is still being elucidated. This paper reviews articles from 1997 to 2017 and reviews the settings, results, and outcomes of SDM in various clinical settings including diabetic macular edema, branch retinal vein occlusion, central serous Chorioretinopathy, proliferative diabetic retinopathy, and age-related macular degeneration.

scholarly journals Antioxidant Role of PRGF on RPE Cells after Blue Light Insult as a Therapy for Neurodegenerative Diseases

2020 ◽  
Vol 21 (3) ◽  
pp. 1021 ◽  
Author(s):  
Carlota Suárez-Barrio ◽  
Susana del Olmo-Aguado ◽  
Eva García-Pérez ◽  
María de la Fuente ◽  
Francisco Muruzabal ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Human Cell Line ◽  
Antioxidant Effect ◽  
Age Related Macular Degeneration ◽  
Strong Impact ◽  
Retinal Diseases ◽  
Age Related ◽  
Gene And Protein Expression

Oxidative stress has a strong impact on the development of retinal diseases such as age-related macular degeneration (AMD). Plasma rich in growth factors (PRGF) is a novel therapeutic approach in ophthalmological pathologies. The aim of this study was to analyze the antioxidant effect of PRGF in retinal epithelial cells (EPR) in in vitro and ex vivo retinal phototoxicity models. In vitro analyses were performed on ARPE19 human cell line. Viability and mitochondrial status were assessed in order to test the primary effects of PRGF. GSH level, and protein and gene expression of the main antioxidant pathway (Keap1, Nrf2, GCL, HO-1, and NQO1) were also studied. Ex vivo analyses were performed on rat RPE, and HO-1 and Nrf2 gene and protein expression were evaluated. The results show that PRGF reduces light insult by stimulating the cell response against oxidative damage and modulates the antioxidant pathway. We conclude that PRGF’s protective effect could prove useful as a new therapy for treating neurodegenerative disorders such as AMD.

scholarly journals Activation of JNK signaling promotes all-trans-retinal–induced photoreceptor apoptosis in mice

2020 ◽  
Vol 295 (20) ◽  
pp. 6958-6971
Author(s):  
Chunyan Liao ◽  
Binxiang Cai ◽  
Yufeng Feng ◽  
Jingmeng Chen ◽  
Yiping Wu ◽  
...  
Keyword(s):  
Dna Damage ◽  
Intraperitoneal Administration ◽  
Photoreceptor Cells ◽  
Age Related Macular Degeneration ◽  
Jnk Signaling ◽  
Age Related ◽  
Dry Amd ◽  
Induced Apoptosis ◽  
Jnk Activation ◽  
Species Production

Disrupted clearance of all-trans-retinal (atRAL), a component of the visual (retinoid) cycle in the retina, may cause photoreceptor atrophy in autosomal recessive Stargardt disease (STGD1) and dry age-related macular degeneration (AMD). However, the mechanisms underlying atRAL-induced photoreceptor loss remain elusive. Here, we report that atRAL activates c-Jun N-terminal kinase (JNK) signaling at least partially through reactive oxygen species production, which promoted mitochondria-mediated caspase- and DNA damage-dependent apoptosis in photoreceptor cells. Damage to mitochondria in atRAL-exposed photoreceptor cells resulted from JNK activation, leading to decreased expression of Bcl2 apoptosis regulator (Bcl2), increased Bcl2 antagonist/killer (Bak) levels, and cytochrome c (Cyt c) release into the cytosol. Cytosolic Cyt c specifically provoked caspase-9 and caspase-3 activation and thereby initiated apoptosis. Phosphorylation of JNK in atRAL-loaded photoreceptor cells induced the appearance of γH2AX, a sensitive marker for DNA damage, and was also associated with apoptosis onset. Suppression of JNK signaling protected photoreceptor cells against atRAL-induced apoptosis. Moreover, photoreceptor cells lacking Jnk1 and Jnk2 genes were more resistant to atRAL-associated cytotoxicity. The Abca4−/−Rdh8−/− mouse model displays defects in atRAL clearance that are characteristic of STGD1 and dry AMD. We found that JNK signaling was activated in the neural retina of light-exposed Abca4−/−Rdh8−/− mice. Of note, intraperitoneal administration of JNK–IN-8, which inhibits JNK signaling, effectively ameliorated photoreceptor degeneration and apoptosis in light-exposed Abca4−/−Rdh8−/− mice. We propose that pharmacological inhibition of JNK signaling may represent a therapeutic strategy for preventing photoreceptor loss in retinopathies arising from atRAL overload.

scholarly journals Neuroprotective Potential of Ginkgo biloba in Retinal Diseases

Planta Medica ◽  
2019 ◽  
Vol 85 (17) ◽  
pp. 1292-1303 ◽  
Author(s):  
Isabel Martínez-Solís ◽  
Nuria Acero ◽  
Francisco Bosch-Morell ◽  
Encarna Castillo ◽  
María Eugenia González-Rosende ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Ginkgo Biloba ◽  
Redox Homeostasis ◽  
Antioxidant Properties ◽  
Retinal Disease ◽  
Age Related Macular Degeneration ◽  
Retinal Diseases ◽  
Age Related ◽  
The Central Nervous System ◽  
Degenerative Processes

AbstractLike other tissues of the central nervous system, the retina is susceptible to damage by oxidative processes that result in several neurodegenerative disease such as age-related macular degeneration, diabetic retinopathy, glaucoma, ischaemic retinal disease, retinal disease produced by light oxidation, and detached retina, among other diseases. The use of antioxidant substances is a solution to some health problems caused by oxidative stress, because they regulate redox homeostasis and reduce oxidative stress. This is important for neurodegeneration linked to oxidation processes. In line with this, Ginkgo biloba is a medicinal plant with excellent antioxidant properties whose effects have been demonstrated in several degenerative processes, including retinal diseases associated with neurodegeneration. This review describes the current literature on the role of ginkgo in retinal diseases associated with neurodegeneration. The information leads to the conclusion that G. biloba extracts might be a good option to improve certain neurodegenerative retinal diseases, but more research is needed to determine the safety and efficacy of G. biloba in these retinal degenerative processes.

scholarly journals Pattern of blindness in a community based hospital of Nepal

2013 ◽  
Vol 5 (1) ◽  
pp. 50-56
Author(s):  
R Sharma ◽  
S Marasini ◽  
BP Nepal
Keyword(s):  
Age Related Macular Degeneration ◽  
Easy Access ◽  
Retinal Diseases ◽  
Access To Health Services ◽  
Community Based ◽  
Cross Sectional ◽  
Age Related ◽  
Access To Health ◽  
Disease Pattern ◽  
The Mean

Introduction: Because of the availability of modern health facilities and moderately easy access to health services in the last 25 years, the blindness due to cataract and trachoma is expected to decline in Nepal. So it is felt that the causes of blindness need to be revised. Objective: To regroup the disease pattern leading to permanent blindness in patients attending a suburban multidisciplinary community-based hospital of Nepal. Materials and methods: A cross-sectional, descriptive study was conducted in patients attending Dhulikhel hospital over a period of 12 months, from March 2010. Only the patients with best corrected visual acuity of < 3/60 were enrolled in the study. A detailed ocular examination was carried out. Results: A total of 76 eyes of 58 patients were analyzed. Of all, 32 were male (55.2 %). The mean age of the patients was 43.03 ± 22.98, with a range of 7 years to 84 years. Retinal diseases had the higher prevalence (23, 39.7 %) followed by amblyopia (10, 17.2 %) and corneal diseases (9, 15.51 %). Anisometropic amblyopia (3.94 %) was the commonest type of amblyopia. Retinitis pigmentosa (9.21 %) and age-related macular degeneration (7.89 %) were common retinal diseases whereas anterior staphyloma (5.26 %) and leucoma (3.94 %) were common corneal diseases. Other important and rare causes of blindness included ethambutol-induced optic neuropathy and vitelliform dystrophy. Conclusion: Periodic collection of statistics on the relative frequency of the causes of blindness is important in socioeconomically developing nations like Nepal. This helps to revise the pattern of blinding diseases so that priorities can be redefined. Nepal J Ophthalmol 2013; 5(9):50-56 DOI: http://dx.doi.org/10.3126/nepjoph.v5i1.7822

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