scholarly journals A review of recent developments in retinitis pigmentosa genetics, its clinical features, and natural course

2021 ◽  
Vol 9 (4) ◽  
Author(s):  
Eleftherios Loukovitis ◽  
Stoimeni Anastasia ◽  
Paris Tranos ◽  
Miltos Balidis ◽  
Solon Asteriadis ◽  
...  
Keyword(s):  
Retinitis Pigmentosa ◽  
Clinical Features ◽  
English Language ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Usher Syndrome ◽  
Retinal Dystrophy ◽  
Clinical Manifestations ◽  
Natural Course ◽  
Recent Developments

Background: Retinitis pigmentosa (RP), an inherited degenerative ocular disease, is considered the most common type of retinal dystrophy. Abnormalities of the photoreceptors, particularly the rods, and of the retinal pigment epithelium, characterizes this disease. The abnormalities progress from the midperiphery to the central retina. We here reviewed the developments in RP genetics in the last decade, along with its clinical features and natural course. Methods: The present review focused on articles in English language published between January 2008 and February 2020, and deposited in PubMed and Google Scholar databases. We searched for articles reporting on the clinical manifestations and genes related to both syndromic and non-syndromic RP. We screened and analyzed 139 articles, published in the last decade, referring to RP pathogenesis and identified, summarized, and highlighted the most significant genes implicated in either syndromic or non-syndromic RP pathogenesis, causing different clinical manifestations. Results: Recent literature revealed that approximately 80 genes are implicated in non-syndromic RP, and 30 genes in syndromic forms, such as Usher syndrome and Bardet‒Biedl syndrome (BBS). Moreover, it is estimated that 27 genes are implicated in autosomal dominant RP (adRP), 55 genes in autosomal recessive RP (arRP), and 6 genes in X-linked RP (xlRP), causing different RP phenotypes. Characteristically, RHO is the most prevalent adRP- and arRP-causing gene, and RPGR the most common xlRP-causing gene. Other important genes are PRPH2, RP1, CRX, RPE65, ABCA4, CRB1, and USH2Α. However, different phenotypes can also be caused by mutations in the same gene. Conclusions: The genetic heterogeneity of RP necessitates further study to map the exact mutations that cause more severe forms of RP, and to develop and use appropriate genetic or other effective therapies in future.

scholarly journals USH2A-Related Retinitis Pigmentosa: Staging of Disease Severity and Morpho-Functional Studies

Diagnostics ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 213
Author(s):  
Benedetto Falsini ◽  
Giorgio Placidi ◽  
Elisa De Siena ◽  
Maria Cristina Savastano ◽  
Angelo Maria Minnella ◽  
...  
Keyword(s):  
Retinitis Pigmentosa ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Usher Syndrome ◽  
Collaborative Study ◽  
Staging System ◽  
International Standards ◽  
Full Field ◽  
Functional Studies ◽  
Cumulative Score

Usher syndrome type 2A (USH2A) is a genetic disease characterized by bilateral neuro-sensory hypoacusia and retinitis pigmentosa (RP). While several methods, including electroretinogram (ERG), describe retinal function in USH2A patients, structural alterations can be assessed by optical coherence tomography (OCT). According to a recent collaborative study, RP can be staged considering visual acuity, visual field area and ellipsoid zone (EZ) width. The aim of this study was to retrospectively determine RP stage in a cohort of patients with USH2A gene variants and to correlate the results with age, as well as additional functional and morphological parameters. In 26 patients with established USH2A genotype, RP was staged according to recent international standards. The cumulative staging score was correlated with patients’ age, amplitude of full-field and focal flicker ERGs, and the OCT-measured area of sub-Retinal Pigment Epithelium (RPE) illumination (SRI). RP cumulative score (CS) was positively correlated (r = 0.6) with age. CS was also negatively correlated (rho = −0.7) with log10 ERG amplitudes and positively correlated (r = 0.5) with SRI. In USH2A patients, RP severity score is correlated with age and additional morpho-functional parameters not included in the international staging system and can reliably predict their abnormality at different stages of disease.

Expanding the retinal phenotype of RP1: from retinitis pigmentosa to a novel and singular macular dystrophy

2019 ◽  
Vol 104 (2) ◽  
pp. 173-181 ◽  
Author(s):  
Marina Riera ◽  
Víctor Abad-Morales ◽  
Rafael Navarro ◽  
Sheila Ruiz-Nogales ◽  
Pilar Méndez-Vendrell ◽  
...  
Keyword(s):  
Visual Acuity ◽  
Retinitis Pigmentosa ◽  
Pigment Epithelium ◽  
Fundus Autofluorescence ◽  
Retinal Pigment ◽  
Retinal Dystrophy ◽  
Macular Dystrophy ◽  
Nucleotide Polymorphisms ◽  
Autofluorescence Imaging ◽  
New Genotype

PurposeThis study aimed to identify the underlying genetic cause(s) of inherited retinal dystrophy (IRD) in 12 families of Kuwaiti origin affected by macular dystrophy and four Spanish patients affected by retinitis pigmentosa (RP).MethodsClinical diagnoses were based on standard ophthalmic evaluations (best-corrected visual acuity, retinography, fundus autofluorescence imaging, optical coherence tomography, electroretinography and visual field tests). Panel-based whole exome sequencing was used to simultaneously analyse 224 IRD genes in one affected member of each family. The putative causative variants were confirmed by Sanger sequencing and cosegregation analyses. Haplotype analysis was performed using single nucleotide polymorphisms.ResultsA homozygous missense mutation c.606C>A (p.Asp202Glu) in RP1 was found to be the molecular cause of IRD in all 12 families from Kuwait. These patients exhibited comparable symptoms, including progressive decline in visual acuity since adolescence. Fundus autofluorescence images revealed bilateral macular retinal pigment epithelium disturbances, with neither perimacular flecks nor peripheral alterations. A shared haplotype spanning at least 1.1 Mb was identified in all families, suggesting a founder effect. Furthermore, RP1 variants involving nonsense and/or frameshifting mutations (three of them novel) were identified in three Spanish autosomal-recessive RP families and one dominant RP pedigree.ConclusionThis study describes, for the first time, a macular dystrophy phenotype caused by an RP1 mutation; establishing a new genotype-phenotype correlation in this gene, expanding its mutation spectrum and further highlighting the clinical heterogeneity associated with IRD.

scholarly journals An Update on Gene Therapy for Inherited Retinal Dystrophy: Experience in Leber Congenital Amaurosis Clinical Trials

2021 ◽  
Vol 22 (9) ◽  
pp. 4534
Author(s):  
Wei Chiu ◽  
Ting-Yi Lin ◽  
Yun-Chia Chang ◽  
Henkie Isahwan-Ahmad Mulyadi Lai ◽  
Shen-Che Lin ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Clinical Trials ◽  
Vision Loss ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Retinal Dystrophy ◽  
Clinical Manifestations ◽  
Adeno Associated Virus ◽  
Leber Congenital Amaurosis ◽  
Gene Therapies

Inherited retinal dystrophies (IRDs) are a group of rare eye diseases caused by gene mutations that result in the degradation of cone and rod photoreceptors or the retinal pigment epithelium. Retinal degradation progress is often irreversible, with clinical manifestations including color or night blindness, peripheral visual defects and subsequent vision loss. Thus, gene therapies that restore functional retinal proteins by either replenishing unmutated genes or truncating mutated genes are needed. Coincidentally, the eye’s accessibility and immune-privileged status along with major advances in gene identification and gene delivery systems heralded gene therapies for IRDs. Among these clinical trials, voretigene neparvovec-rzyl (Luxturna), an adeno-associated virus vector-based gene therapy drug, was approved by the FDA for treating patients with confirmed biallelic RPE65 mutation-associated Leber Congenital Amaurosis (LCA) in 2017. This review includes current IRD gene therapy clinical trials and further summarizes preclinical studies and therapeutic strategies for LCA, including adeno-associated virus-based gene augmentation therapy, 11-cis-retinal replacement, RNA-based antisense oligonucleotide therapy and CRISPR-Cas9 gene-editing therapy. Understanding the gene therapy development for LCA may accelerate and predict the potential hurdles of future therapeutics translation. It may also serve as the template for the research and development of treatment for other IRDs.

Major Hereditary Gastrointestinal Cancer Syndromes: a Narrative Review

2017 ◽  
Vol 26 (2) ◽  
pp. 157-163 ◽  
Author(s):  
Lakshmi Manogna Chintalacheruvu ◽  
Trudy Shaw ◽  
Avanija Buddam ◽  
Osama Diab ◽  
Thamer Kassim ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Genetic Testing ◽  
Gastrointestinal Cancer ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Clinical Manifestations ◽  
Micro Rna ◽  
Diffuse Gastric Cancer ◽  
Adenomatous Polyposis ◽  
Cancer Syndromes

Gastrointestinal cancer is one of the major causes of death worldwide. Hereditary gastrointestinal cancer syndromes constitute about 5-10% of all cancers. About 20-25% of undiagnosed cases have a possible hereditary component, which is not yet established. In the last few decades, the advance in genomics has led to the discovery of multiple cancer predisposition genes in gastrointestinal cancer. Physicians should be aware of these syndromes to identify high-risk patients and offer genetic testing to prevent cancer death. In this review, we describe clinical manifestations, genetic testing and its challenges, diagnosis and management of the major hereditary gastrointestinal cancer syndromes.Key words:  −  −  −  − .Abbreviations: ACG: American College of Gastroenterology; AFAP: attenuated FAP; APC: adenomatous polyposis coli; CDH1: E-cadherin; CHRPE: congenital hypertrophy of the retinal pigment epithelium; CRC: colorectal cancer; FAMMM: Familial atypical multiple mole melanoma; FAP: Familial adenomatous polyposis; GC: gastric cancer; HDGC: Hereditary diffuse gastric cancer; IHC: immunohistochemical; IPAA: ileal pouch–anal anastomosis; IRA: ileorectal anastomosis; MSI: microsatellite instability; MMR: mismatch repair; miRNA: micro RNA.

scholarly journals Pathophysiological features of the visual cycle, cascade and metabolic pathways in retinitis pigmentosa

2021 ◽  
Vol 14 (1) ◽  
pp. 80-88
Author(s):  
M. E. Weener ◽  
D. S. Atarshchikov ◽  
V. V. Kadyshev ◽  
I. V. Zolnikova ◽  
A. M. Demchinsky ◽  
...  
Keyword(s):  
Retinal Pigment Epithelium ◽  
Literature Review ◽  
Retinitis Pigmentosa ◽  
Metabolic Pathways ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Visual Signal ◽  
Visual Cycle ◽  
Target Treatment ◽  
Interphotoreceptor Matrix

This literature review offers a detailed description of the genes and proteins involved in pathophysiological processes in isolated retinitis pigmentosa (RP). To date, 84 genes and 7 candidate genes have been described for non-syndromic RP. Each of these genes encodes a protein that plays a role in vital processes in the retina and / or retinal pigment epithelium, including the cascade of phototransduction (transmission of the visual signal), the visual cycle, ciliary transport, the environment of photoreceptor cilia and the interphotoreceptor matrix. The identification and study of pathophysiological pathways affected in non-syndromic RP is important for understanding the main pathogenic ways and developing approaches to target treatment.

Treatments Being Developed in Retinitis Pigmentosa

2021 ◽  
pp. 150-154
Keyword(s):  
Retinitis Pigmentosa ◽  
Retinal Pigment Epithelial ◽  
Vision Loss ◽  
Platelet Rich Plasma ◽  
Retinal Pigment ◽  
Retinal Prostheses ◽  
Pigment Epithelial ◽  
Recent Developments ◽  
Severe Vision Loss ◽  
Experimental Approaches

Recent developments in understanding the pathophysiology of retinitis pigmentosa (RP) have shown that there have been new hopes in the treatment of this disease which can cause severe vision loss. Proven therapy for RP-associated photoreceptor loss and retinal pigment epithelial damage has not yet been reported. New or experimental approaches for the treatment of RP include platelet-rich plasma, gene therapy, transplantation of fetal retinal cells or stem cells, and electronic retinal prostheses.

Diffuse Pigmented Lesions in the Outer Retina: An Unusual Fundus Appearance

2019 ◽  
Vol 4 (3) ◽  
pp. 243-247
Author(s):  
Matthew D. Benson ◽  
Uriel Rubin ◽  
Marvi Cheema ◽  
Ian M. MacDonald ◽  
Matthew T.S. Tennant ◽  
...  
Keyword(s):  
Phenotypic Diversity ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Retinal Dystrophy ◽  
Full Field ◽  
Panel Testing ◽  
Pigmented Lesions ◽  
Hereditary Retinal Dystrophy ◽  
Ultrasound Findings ◽  
Chest X Ray

Purpose: This report describes and provides a differential diagnosis for a patient with unusual bilateral retinal pigmented lesions. Methods: A 40-year-old woman was found to have multiple flat, gray lesions scattered across her fundi, becoming larger and more confluent toward the periphery. There were small drusenlike deposits in her foveae. The hyperpigmented lesions demonstrated hypoautofluorescence with thickening of the retinal pigment epithelium and disruption of the overlying layers on optical coherence tomography (OCT). Full-field electroretinography revealed generalized reduced a- and b-wave amplitudes. Results: Chest x-ray, breast ultrasound, mammography, and pelvic ultrasound findings were negative for malignant etiologic factors. Panel testing results for hereditary retinal dystrophy were negative. Conclusions: Although the clinical and OCT appearance of the lesions is similar to congenital grouped pigmentation, the symmetric and bilateral nature of ocular findings coupled with electroretinographic changes suggest a possible retinal dystrophy. This case adds to the phenotypic diversity of pigmented fundus lesions.

scholarly journals The Role of the Endothelin System in the Vascular Dysregulation Involved in Retinitis Pigmentosa

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Francesco Saverio Sorrentino ◽  
Claudio Bonifazzi ◽  
Paolo Perri
Keyword(s):  
Blood Flow ◽  
Retinitis Pigmentosa ◽  
Vascular System ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Ocular Blood Flow ◽  
The Body ◽  
Vascular Dysregulation ◽  
Endothelin System

Retinitis pigmentosa is a clinical and genetic group of inherited retinal disorders characterized by alterations of photoreceptors and retinal pigment epithelium leading to a progressive concentric visual field restriction, which may bring about severe central vision impairment. Haemodynamic studies in patients with retinitis pigmentosa have demonstrated ocular blood flow abnormalities both in retina-choroidal and in retroocular vascular system. Moreover, several investigations have studied the augmentation of endothelin-1 plasma levels systemically in the body and locally in the eye. This might account for vasoconstriction and ischemia, typical in vascular dysregulation syndrome, which can be considered an important factor of reduction of the ocular blood flow in subjects affected by retinitis pigmentosa.

Transplantation of intact sheets of fetal neural retina with its retinal pigment epithelium in retinitis pigmentosa patients

2002 ◽  
Vol 133 (4) ◽  
pp. 544-550 ◽  
Author(s):  
Norman D Radtke ◽  
Magdalene J Seiler ◽  
Robert B Aramant ◽  
Heywood M Petry ◽  
Diane J Pidwell
Keyword(s):  
Retinal Pigment Epithelium ◽  
Retinitis Pigmentosa ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Neural Retina

scholarly journals Evaluation of Psychophysiological and Hormonal Changes in Acute and Chronic Forms of Central Serous Chorioretinopathy

2019 ◽  
Vol 4 (4) ◽  
pp. 119-123
Author(s):  
A. A. Shchuko ◽  
S. I. Kolesnikov ◽  
T. N. Iurevа ◽  
A. N. Zlobina
Keyword(s):  
Visual System ◽  
Hormonal Regulation ◽  
Central Serous Chorioretinopathy ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Clinical Manifestations ◽  
Role Playing ◽  
Feedback Mechanism ◽  
Pathological Process ◽  
Hormonal Changes

Aim: to evaluate changes in the parameters of the visual system, psycho-physiological reactions (psychoemotional changes), and hormonal changes in patients with central serous chorioretinopathy and on this basis to develop a conceptual scheme for the activation of pathogenetic mechanisms of the formation of acute and chronic forms of the disease. Material and methods. 40 people with central serous chorioretinopathy and 26 control subjects were examined with the assessment of psychophysiological (psychoemotional) and hormonal changes.Results. The most informative criteria have been identified which determine various forms of the clinical course of central serous chorioretinopathy: the area of damage to the retinal pigment epithelium, psycho-emotional changes (the difficulties of role-playing, dependence on other people in domestic and professional environment, a high degree of reactive and personal anxiety, paranoia and level of distress), violation of the psycho-physiological characteristics of the state of the visual system, changes in hormonal regulation (cortisol, thyroid hormones, dehydroepiandrosterone, melatonin, 17-OH-progesterone, testosterone).Conclusion. The complex of psychophysiological changes that form the basis for the pathogenesis of central serous chorioretinopathy, according to the feedback mechanism, enhances the initial moments of the disease, exacerbates the severity of clinical manifestations and leads to chronicity of the pathological process, causing, thus, the complexity of diagnosis and treatment of central serous chorioretinopathy.

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