scholarly journals The quest of vision: retina’s daily challenges

2020 ◽  
Vol 42 (5) ◽  
pp. 4-10
Author(s):  
Dhanach Dhirachaikulpanich ◽  
Robert A.I. Paraoan ◽  
Emil Carlsson ◽  
Luminita Paraoan
Keyword(s):  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Treatment Options ◽  
Cell Monolayer ◽  
Adjacent Cell ◽  
Retinal Diseases ◽  
Physiological Processes ◽  
Visual Processes ◽  
Neuronal Type ◽  
Incoming Light

The retina is a complex biological structure located at the back of the eye. Every day, it continually performs an intricate set of tasks to provide us with the sense of vision. The neuroretina encompasses neuronal type of cells including the light-sensitive photoreceptors, which sense the incoming light and trigger the conversion of the visual stimulus information to a neural response relayed to our brain where images are created. This article focuses on the physiological processes occurring in the retina and the exquisite interplay between photoreceptors and the adjacent cell monolayer called the retinal pigment epithelium, which underpins the key visual processes of phototransduction, visual cycle and phagocytosis of spent photoreceptors’ outer segments. We also present examples of functional defects in the retina and how they lead to impaired vision or blindness, and discuss some emerging treatment options for retinal diseases.

Vitrectomy for Subretinal and Submacular Hemorrhages

2021 ◽  
pp. 39-45
Keyword(s):  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Treatment Options ◽  
Real Life ◽  
Surgical Techniques ◽  
Age Related Macular Degeneration ◽  
Retinal Diseases ◽  
Anti Vegf ◽  
Age Related ◽  
Underlying Pathology

Submacular hemorrhage (SMH) is relatively rare in retinal practice. However, it is an important complication of many choroidal and retinal diseases, particularly neovascular age-related macular degeneration (AMD). When untreated the visual prognosis is poor, especially in patients with AMD, and SMHs cannot be effectively treated with only anti-vascular endothelial growth factor (anti-VEGF) injection. The current therapeutic approach is based upon the displacement of the subretinal hemorrhage away from the central retina as soon as possible. The use of tissue plasminogen activator (tPA) has been an important milestone in the treatment of SMHs. Current vitrectomy techniques for SMH management include subretinal tPA injection and aspiration of the blood, and subretinal tPA, and air/anti-VEGF injection with gas tamponade. Submacular surgery, which involves removal of the SMH and choroidal neovascularization (CNV) through a retinotomy, seems to be a technique reserved for selected cases where central retinal pigment epithelium appears to be undiseased/uninvolved. Among the non-surgical treatment options, pneumatic displacement with intravitreal tPA and gas injection may be preferred especially for small-medium sized and thin SMHs. However, the favored approach in real-life conditions is shaped by the physician's experience and the available treatment options. Regardless of the preferred approach, the continuity of the treatment of the underlying pathology is important. As the underlying pathology is usually a CNV, the continuation of anti-VEGF treatment is important for maintaining the visual gain of the initial treatment and reducing the risk of recurrent SMH. The breakthrough development rate of the drugs and the surgical techniques for the treatment of retinal diseases promises in terms of new and more effective treatment approaches.

scholarly journals Pathogenic Effects of Mineralocorticoid Pathway Activation in Retinal Pigment Epithelium

2021 ◽  
Vol 22 (17) ◽  
pp. 9618
Author(s):  
Jérémie Canonica ◽  
Min Zhao ◽  
Tatiana Favez ◽  
Emmanuelle Gelizé ◽  
Laurent Jonet ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Retinal Pigment Epithelium ◽  
Barrier Function ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Retinal Diseases ◽  
Mesenchymal Transition ◽  
Rpe Cells ◽  
Pathway Activation ◽  
And Migration

Glucocorticoids are amongst the most used drugs to treat retinal diseases of various origins. Yet, the transcriptional regulations induced by glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) activation in retinal pigment epithelium cells (RPE) that form the outer blood–retina barrier are unknown. Levels of endogenous corticoids, ligands for MR and GR, were measured in human ocular media. Human RPE cells derived from induced pluripotent stem cells (iRPE) were used to analyze the pan-transcriptional regulations induced by aldosterone—an MR-specific agonist, or cortisol or cortisol + RU486—a GR antagonist. The retinal phenotype of transgenic mice that overexpress the human MR (P1.hMR) was analyzed. In the human eye, the main ligand for GR and MR is cortisol. The iRPE cells express functional GR and MR. The subset of genes regulated by aldosterone and by cortisol + RU-486, and not by cortisol alone, mimics an imbalance toward MR activation. They are involved in extracellular matrix remodeling (CNN1, MGP, AMTN), epithelial–mesenchymal transition, RPE cell proliferation and migration (ITGB3, PLAUR and FOSL1) and immune balance (TNFSF18 and PTX3). The P1.hMR mice showed choroidal vasodilation, focal alteration of the RPE/choroid interface and migration of RPE cells together with RPE barrier function alteration, similar to human retinal diseases within the pachychoroid spectrum. RPE is a corticosteroid-sensitive epithelium. MR pathway activation in the RPE regulates genes involved in barrier function, extracellular matrix, neural regulation and epithelial differentiation, which could contribute to retinal pathology.

Normative pattern and determinants of outer retinal thickness in an Asian population: the Singapore Epidemiology of Eye Diseases Study

2019 ◽  
Vol 103 (10) ◽  
pp. 1406-1412 ◽  
Author(s):  
Wei Dai ◽  
Yih-Chung Tham ◽  
Miao-Li Chee ◽  
Shivani Majithia ◽  
Nicholas Y Q Tan ◽  
...  
Keyword(s):  
Retinal Thickness ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Plexiform Layer ◽  
Asian Population ◽  
Final Analysis ◽  
Population Based ◽  
Eye Diseases ◽  
Retinal Diseases ◽  
Sd Oct

Background/aimsTo evaluate the distribution and determinants of outer retinal thickness in eyes without retinal diseases, using spectral-domain optical coherence tomography (SD-OCT).MethodsParticipants were recruited from the Singapore Epidemiology of Eye Diseases Study, a population-based study among Chinese, Malays and Indians in Singapore. A total of 5333 participants underwent SD-OCT imaging in which a 6×6 mm2 measurement area centred at the fovea. Outer retinal thickness was defined as the distance from the outer plexiform layer to the retinal pigment epithelium layer boundary.Results7444 eyes from 4454 participants were included in final analysis. Of them, mean age was 58.4 years (SD 8.3), and 2294 (51.5%) were women. Women (121.0±8.1 µm) had thinner average outer retinal thickness than men (125.6±8.2 µm) (p<0.001). Malays (121.4±8.7 µm) had thinner average outer retinal thickness than Indians (124.3±8.6 µm) and Chinese (123.7±7.9 µm) (both p<0.001). In multivariable models, thinner average outer retinal thickness was associated with older age (per decade, β=−1.02, p<0.001), hypertension (β=−0.59, p=0.029), diabetes (β=−0.73, p=0.013), chronic kidney disease (β=−1.25, p=0.017), longer axial length (per mm, β=−0.76, p<0.001), flatter corneal curvature (per mm, β=−2.00, p<0.001) and higher signal strength (β=−1.46, p<0.001).ConclusionIn this large sample of Asian population, we provided normative SD-OCT data on outer retinal thickness in eyes without retinal diseases. Women had thinner outer retina than men. For the first time, these findings provide fundamental knowledge on normative profile of outer retinal thickness in Asians.

Diagnosis and treatment of peripheral exudative haemorrhagic chorioretinopathy

2019 ◽  
Vol 104 (6) ◽  
pp. 874-878 ◽  
Author(s):  
Sarah Vandefonteyne ◽  
Jean-Pierre Caujolle ◽  
Laurence Rosier ◽  
John Conrath ◽  
Gabriel Quentel ◽  
...  
Keyword(s):  
Visual Acuity ◽  
Multimodal Imaging ◽  
Chart Review ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Choroidal Melanoma ◽  
Endothelial Growth Factor

PurposePeripheral exudative haemorrhagic chorioretinopathy (PEHCR) is a rare disorder that is often misdiagnosed. The aim of this study was to better characterise PEHCR and to assess treatment options.Material and methodsRetrospective multicentric chart review.ResultsOf 84 eyes (69 patients) with PEHCR referred between 2005 and 2017, the most common referral diagnosis was choroidal melanoma (41.3%). Bilateral involvement was found in 21.7% of cases. Haemorrhagic retinal pigment epithelium detachment was the most common peripheral lesion (53.6%). Maculopathy was associated with peripheral lesions in 65.8% of cases. PEHCR lesions were mostly heterogeneous (58.8%) on B-scan ultrasonography. Choroidal neovascularisation was found in 10 eyes (26.3%) out of 38 eyes that underwent fluorescein angiography. Polyps were observed in 14 eyes (58.3%) out of 24 eyes that underwent indocyanine green angiography. Fifty-one eyes were treated (62.2%). Intravitreal injections (IVTI) of antivascular endothelial growth factor (VEGF) were the most used treatment (36.6%) before laser photocoagulation, photodynamic therapy, vitrectomy and cryotherapy. Only vitrectomy improved visual acuity. Most lesions (65.6%) regressed at the last follow-up visit.ConclusionIn case of PEHCR, multimodal imaging is useful to avoid misdiagnosis, to characterise PEHCR lesions and to guide treatment strategies. Regression of PEHCR lesions was observed in two-thirds of the patients. Vitrectomy improved visual acuity. More than a third of patients underwent anti-VEGF IVTI. Further studies are needed to assess IVTI’s efficacy.

Identification of sodium channel subtypes induced in cultured retinal pigment epithelium cells

1995 ◽  
Vol 12 (5) ◽  
pp. 1001-1005 ◽  
Author(s):  
Heather Dawes ◽  
Gail Mandel ◽  
Gary Matthews
Keyword(s):  
Retinal Pigment Epithelium ◽  
Sodium Channel ◽  
Sodium Current ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Rpe Cells ◽  
Voltage Dependent ◽  
Dissociated Cell Culture ◽  
Epithelium Cells ◽  
Neuronal Type

AbstractRecent electrophysiological experiments have shown that retinal pigment epithelium (RPE) cells begin to produce neuronal-type voltage-dependent sodium currents when placed in dissociated cell culture. In this study, the sodium channel types induced in cultured rat RPE cells were identified. Sodium channel mRNAs encoding two distinct alpha subunits were detected in the cultured RPE cells, brain type II/IIA, and a novel rat mRNA which we have termed RET1. These two sodium channel types may correspond to the TTX-sensitive and TTX-insensitive components of sodium current reported previously in cultured rat RPE cells.

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 The Cytoskeleton of the Retinal Pigment Epithelium: from Normal Aging to Age-Related Macular Degeneration

2019 ◽  
Vol 20 (14) ◽  
pp. 3578 ◽  
Author(s):  
Ioana-Sandra Tarau ◽  
Andreas Berlin ◽  
Christine A. Curcio ◽  
Thomas Ach
Keyword(s):  
Retinal Pigment Epithelium ◽  
Macular Degeneration ◽  
Current Knowledge ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Complex Structure ◽  
Age Related Macular Degeneration ◽  
Retinal Diseases ◽  
Strong Connection ◽  
Age Related

The retinal pigment epithelium (RPE) is a unique epithelium, with major roles which are essential in the visual cycle and homeostasis of the outer retina. The RPE is a monolayer of polygonal and pigmented cells strategically placed between the neuroretina and Bruch membrane, adjacent to the fenestrated capillaries of the choriocapillaris. It shows strong apical (towards photoreceptors) to basal/basolateral (towards Bruch membrane) polarization. Multiple functions are bound to a complex structure of highly organized and polarized intracellular components: the cytoskeleton. A strong connection between the intracellular cytoskeleton and extracellular matrix is indispensable to maintaining the function of the RPE and thus, the photoreceptors. Impairments of these intracellular structures and the regular architecture they maintain often result in a disrupted cytoskeleton, which can be found in many retinal diseases, including age-related macular degeneration (AMD). This review article will give an overview of current knowledge on the molecules and proteins involved in cytoskeleton formation in cells, including RPE and how the cytoskeleton is affected under stress conditions—especially in AMD.

scholarly journals Scaffolds for retinal pigment epithelial cell transplantation in age-related macular degeneration

2017 ◽  
Vol 8 ◽  
pp. 204173141772084 ◽  
Author(s):  
Corina E White ◽  
Ronke M Olabisi
Keyword(s):  
Retinal Pigment Epithelium ◽  
Macular Degeneration ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Cell Monolayer ◽  
Age Related Macular Degeneration ◽  
Artificial Substrates ◽  
Age Related ◽  
Retinal Pigment Epithelium Cells ◽  
Epithelium Cells

In several retinal degenerative diseases, including age-related macular degeneration, the retinal pigment epithelium, a highly functionalized cell monolayer, becomes dysfunctional. These retinal diseases are marked by early retinal pigment epithelium dysfunction reducing its ability to maintain a healthy retina, hence making the retinal pigment epithelium an attractive target for treatment. Cell therapies, including bolus cell injections, have been investigated with mixed results. Since bolus cell injection does not promote the proper monolayer architecture, scaffolds seeded with retinal pigment epithelium cells and then implanted have been increasingly investigated. Such cell-seeded scaffolds address both the dysfunction of the retinal pigment epithelium cells and age-related retinal changes that inhibit the efficacy of cell-only therapies. Currently, several groups are investigating retinal therapies using seeded cells from a number of cell sources on a variety of scaffolds, such as degradable, non-degradable, natural, and artificial substrates. This review describes the variety of scaffolds that have been developed for the implantation of retinal pigment epithelium cells.

scholarly journals The Interplay between Peripherin 2 Complex Formation and Degenerative Retinal Diseases

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 784 ◽  
Author(s):  
Lars Tebbe ◽  
Mashal Kakakhel ◽  
Mustafa S. Makia ◽  
Muayyad R. Al-Ubaidi ◽  
Muna I. Naash
Keyword(s):  
Complex Formation ◽  
Mouse Models ◽  
Outer Segment ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Fine Tuning ◽  
Current Status ◽  
Retinal Diseases ◽  
Choroidal Vasculature ◽  
And Function

Peripherin 2 (Prph2) is a photoreceptor-specific tetraspanin protein present in the outer segment (OS) rims of rod and cone photoreceptors. It shares many common features with other tetraspanins, including a large intradiscal loop which contains several cysteines. This loop enables Prph2 to associate with itself to form homo-oligomers or with its homologue, rod outer segment membrane protein 1 (Rom1) to form hetero-tetramers and hetero-octamers. Mutations in PRPH2 cause a multitude of retinal diseases including autosomal dominant retinitis pigmentosa (RP) or cone dominant macular dystrophies. The importance of Prph2 for photoreceptor development, maintenance and function is underscored by the fact that its absence results in a failure to initialize OS formation in rods and formation of severely disorganized OS membranous structures in cones. Although the exact role of Rom1 has not been well studied, it has been concluded that it is not necessary for disc morphogenesis but is required for fine tuning OS disc size and structure. Pathogenic mutations in PRPH2 often result in complex and multifactorial phenotypes, involving not just photoreceptors, as has historically been reasoned, but also secondary effects on the retinal pigment epithelium (RPE) and retinal/choroidal vasculature. The ability of Prph2 to form complexes was identified as a key requirement for the development and maintenance of OS structure and function. Studies using mouse models of pathogenic Prph2 mutations established a connection between changes in complex formation and disease phenotypes. Although progress has been made in the development of therapeutic approaches for retinal diseases in general, the highly complex interplay of functions mediated by Prph2 and the precise regulation of these complexes made it difficult, thus far, to develop a suitable Prph2-specific therapy. Here we describe the latest results obtained in Prph2-associated research and how mouse models provided new insights into the pathogenesis of its related diseases. Furthermore, we give an overview on the current status of the development of therapeutic solutions.

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