scholarly journals Mitochondrial Retinopathies

2021 ◽  
Vol 23 (1) ◽  
pp. 210
Author(s):  
Massimo Zeviani ◽  
Valerio Carelli
Keyword(s):  
Retinitis Pigmentosa ◽  
Optic Atrophy ◽  
Large Scale ◽  
Autosomal Recessive ◽  
Retinal Dystrophy ◽  
Nuclear Gene ◽  
Leigh Syndrome ◽  
Recessive Mutations ◽  
Genetic Abnormalities ◽  
Cardinal Symptom

The retina is an exquisite target for defects of oxidative phosphorylation (OXPHOS) associated with mitochondrial impairment. Retinal involvement occurs in two ways, retinal dystrophy (retinitis pigmentosa) and subacute or chronic optic atrophy, which are the most common clinical entities. Both can present as isolated or virtually exclusive conditions, or as part of more complex, frequently multisystem syndromes. In most cases, mutations of mtDNA have been found in association with mitochondrial retinopathy. The main genetic abnormalities of mtDNA include mutations associated with neurogenic muscle weakness, ataxia and retinitis pigmentosa (NARP) sometimes with earlier onset and increased severity (maternally inherited Leigh syndrome, MILS), single large-scale deletions determining Kearns–Sayre syndrome (KSS, of which retinal dystrophy is a cardinal symptom), and mutations, particularly in mtDNA-encoded ND genes, associated with Leber hereditary optic neuropathy (LHON). However, mutations in nuclear genes can also cause mitochondrial retinopathy, including autosomal recessive phenocopies of LHON, and slowly progressive optic atrophy caused by dominant or, more rarely, recessive, mutations in the fusion/mitochondrial shaping protein OPA1, encoded by a nuclear gene on chromosome 3q29.

scholarly journals Targeting of the NRL Pathway as a Therapeutic Strategy to Treat Retinitis Pigmentosa

2020 ◽  
Vol 9 (7) ◽  
pp. 2224 ◽  
Author(s):  
Spencer M. Moore ◽  
Dorota Skowronska-Krawczyk ◽  
Daniel L. Chao
Keyword(s):  
Retinitis Pigmentosa ◽  
Autosomal Recessive ◽  
Therapeutic Strategy ◽  
Leucine Zipper ◽  
Retinal Dystrophy ◽  
Rod Photoreceptor ◽  
Cone Photoreceptor ◽  
Future Directions ◽  
Inherited Retinal Dystrophy ◽  
Visual Acuity Loss

Retinitis pigmentosa (RP) is an inherited retinal dystrophy (IRD) with a prevalence of 1:4000, characterized by initial rod photoreceptor loss and subsequent cone photoreceptor loss with accompanying nyctalopia, visual field deficits, and visual acuity loss. A diversity of causative mutations have been described with autosomal dominant, autosomal recessive, and X-linked inheritance and sporadic mutations. The diversity of mutations makes gene therapy challenging, highlighting the need for mutation-agnostic treatments. Neural leucine zipper (NRL) and NR2E3 are factors important for rod photoreceptor cell differentiation and homeostasis. Germline mutations in NRL or NR2E3 leads to a loss of rods and an increased number of cones with short wavelength opsin in both rodents and humans. Multiple groups have demonstrated that inhibition of NRL or NR2E3 activity in the mature retina could endow rods with certain properties of cones, which prevents cell death in multiple rodent RP models with diverse mutations. In this review, we summarize the literature on NRL and NR2E3, therapeutic strategies of NRL/NR2E3 modulation in preclinical RP models, as well as future directions of research. In summary, inhibition of the NRL/NR2E3 pathway represents an intriguing mutation agnostic and disease-modifying target for the treatment of RP.

scholarly journals Senior Loken syndrome with Atypical Retinitis Pigmentosa: a rare manifestation of rare disease

2018 ◽  
Vol 5 (2) ◽  
pp. 651
Author(s):  
Madhura S. ◽  
Sowrabha . ◽  
Manjunath . ◽  
Savitha M. R.
Keyword(s):  
Renal Transplantation ◽  
Retinitis Pigmentosa ◽  
Autosomal Recessive ◽  
Retinal Dystrophy ◽  
Rare Condition ◽  
End Stage Kidney Disease ◽  
Rare Manifestation ◽  
Autosomal Recessive Condition ◽  
Urinary Concentrating Ability ◽  
End Stage

Senior Loken syndrome is an autosomal recessive condition characterized by combination of nephronophthisis and retinal degeneration. The earliest presenting features include polyuria and polydipsia secondary to impaired urinary concentrating ability. Nephronophthisis progresses to end stage kidney disease (ESKD) during second decade. The treatment of choice for ESKD due to nephronophthisis is renal transplantation. Retinal lesions are variable ranging from severe infantile onset retinal dystrophy to more typical retinitis pigmentosa. There is a spectrum of other features associated with this condition including skeletal, dermatological and cerebellar anomalies. Till date very few cases have been reported due to lack of awareness of this rare condition. Here, we report a case of Senior loken syndrome with atypical retinitis pigmentosa in a 14-year-old boy.

scholarly journals Autosomal-Recessive Mutations in AP3B2 , Adaptor-Related Protein Complex 3 Beta 2 Subunit, Cause an Early-Onset Epileptic Encephalopathy with Optic Atrophy

2016 ◽  
Vol 99 (6) ◽  
pp. 1368-1376 ◽  
Author(s):  
Mirna Assoum ◽  
Christophe Philippe ◽  
Bertrand Isidor ◽  
Laurence Perrin ◽  
Periklis Makrythanasis ◽  
...  
Keyword(s):  
Optic Atrophy ◽  
Protein Complex ◽  
Early Onset ◽  
Autosomal Recessive ◽  
Epileptic Encephalopathy ◽  
Related Protein ◽  
Recessive Mutations ◽  
Beta 2

scholarly journals Variant Profiling of a Large Cohort of 138 Chinese Families With Autosomal Dominant Retinitis Pigmentosa

2021 ◽  
Vol 8 ◽  
Author(s):  
Ting Xiao ◽  
Yue Xie ◽  
Xin Zhang ◽  
Ke Xu ◽  
Xiaohui Zhang ◽  
...  
Keyword(s):  
Retinitis Pigmentosa ◽  
Autosomal Recessive ◽  
Autosomal Dominant ◽  
Retinal Dystrophy ◽  
Large Cohort ◽  
Chinese Patients ◽  
Screening Methods ◽  
Compound Heterozygous ◽  
Dominant Trait ◽  
Essential Information

Retinitis pigmentosa (RP) is the most common form of inherited retinal dystrophy, and 15–25% of RP is transmitted as an autosomal dominant (ad) trait. The objectives of this study were to establish the variant profile in a large cohort of adRP families and to elucidate the variant spectrum of each adRP gene in Chinese patients. A total of 138 probands clinically diagnosed with RP as a presumed autosomal dominant trait were recruited. All probands underwent ophthalmic examinations by specialists. A combination of molecular screening methods, including targeted next-generation sequencing, Sanger DNA sequencing, and multiplex ligation probe amplification assay, was used to detect variants. We identified heterozygous variants of 11 adRP genes in 73 probands, hemizygous, or heterozygous variants of X-linked RP genes in six patients, compound heterozygous variants of autosomal recessive RP genes in three pseudodominant families, and one heterozygous variant of one ad cone and rod dystrophy gene in one proband. One proband was found carrying both variants in RPGR and FAM161A. The overall detection rate was 59.4% (82/138). We detected 72 distinct disease-causing variants involving 16 RP genes and one cone-rod dystrophy gene; 33 of these variants have not been reported previously. Disease-causing variants were identified in the adRP genes in 52.9% of the families, followed by 4.3% in the X-linked RP genes, and 2.2% in the autosomal recessive genes. The most frequent mutant genes were RHO, PRPF31, RP1, SNRNP200, and PRPF8, which explained up to 78.0% of the genetically diagnosed families. Most of the variants identified in adRP genes were missense, and copy number variations were common (7/20) in the PRPF31 gene. We established the profile of the mutated genes and the variant spectrum of adRP genes in a large cohort of Chinese patients, providing essential information for genetic counseling and future development of therapeutics for retinal dystrophy inherited as a dominant trait.

scholarly journals BILATERAL IRREVERSIBLE BLINDNESS

2014 ◽  
Vol 21 (06) ◽  
pp. 1258-1263
Author(s):  
Asif Iqbal ◽  
Muhammad Idrees ◽  
Bilal Bashir ◽  
Mubashir Rehman ◽  
Omer Khan Orakzai
Keyword(s):  
Retinitis Pigmentosa ◽  
Optic Atrophy ◽  
Retinal Dystrophy ◽  
Age Groups ◽  
Corneal Edema ◽  
Corneal Opacity ◽  
Congenital Glaucoma ◽  
Congenital Diseases ◽  
Primary Glaucoma ◽  
Irreversible Blindness

Objective: To find out the causes of bilateral irreversible blindness in patients of different age groups in District Swabi. Design: It is a prospective observational study of one hundred and eighty nine consecutive blind cases. Place and Duration of Study: The study was conducted from July 2010 to June, 2012 at the Ophthalmology Department of District Headquarter Hospital, Swabi. Subjects and Methods: Informed consent was taken from the patient or guardian of the patient. Patients fulfilling inclusion and exclusion criteria were included in the study. A standard proforma was designed and entries were made regarding present, past and family history, thorough ocular examination of every patient was performed on slit-lamp with relevant biomicroscopic aids and posterior segment examination was conducted with direct as well as indirect ophthalmoscope. Biomicroscopy was performed as and when required. lntraocular pressure using schiotz tonometer, corneal diameters, retinoscopy and ocular mobility were noted and relevant investigations were performed when needed. Children and mentally retarded patients were examined using short general anaesthesia. Results: Of 189 patients 61.4% were males and 38.6% were females. Congenital Causes were present in 49.7% and acquired causes in 50.3%. Diseases accounted for 88.9%, trauma in 10.1% and unknown causes in 1.1% cases. Congenital diseases included congenital glaucoma in 35.1%, retinitis pigmentosa in 29.7% and albinism in 19.1% cases. Acquired diseases included primary glaucoma in 33.8%, diabetic retinopathy 23 %, secondary glaucoma in 17.5% and childhood infection in 10.8% cases. Corneal findings included corneal opacity in 31.2%, corneal edema in 4.8% and absent cornea in 7.4%. Optic nerve findings included optic atrophy in 16.4%, glaucomatous optic atrophy in 16.9%, new vessels in 9.5%. Retina findings included retinal dystrophy in 14.3%, maculopathy in 5.3%, chorioretinopathy in 0.5%, vascular retinopathy and hypopigmentation in 9.5% each respectively. Conclusions: Irreversible blindness is more common in children and young adults and mostly males are affected. Glaucoma is the commonest cause followed by retinitis pigmentosa and albinism in this study.

Ayurvedic management of Retinitis Pigmentosa (Doshandha) - A Case Study

2017 ◽  
Vol 2 (05) ◽  
Author(s):  
Anju D. ◽  
Pushpa Raj Poudel ◽  
Ajoy Viswam ◽  
Ashwini M. J.
Keyword(s):  
Retinitis Pigmentosa ◽  
Low Vision ◽  
Symptomatic Relief ◽  
Retinal Dystrophy ◽  
Treatment Protocol ◽  
Signs And Symptoms ◽  
Photoreceptor Cells ◽  
Rod Photoreceptor ◽  
Night Time ◽  
Initial Symptoms

Retinitis pigmentosa (RP) is an inherited, degenerative eye disease that causes severe vision impairment due to the progressive degeneration of rod photoreceptor cells in retina. This form of retinal dystrophy manifests initial symptoms independentof age; thus, RP diagnosis occurs anywhere from early infancy to late adulthood. This primary pigmentary retinal dystrophy is a hereditary disorder predominantly affecting the rods more than the cones. The main classical triads of retinitis pigmentosa are arteriolar attenuation, Retinal bone spicule pigmentation and Waxy disc pallor. The main treatment of retinitis pigmentosa is by using Low vision aids (LVA) and Genetic counseling. As such a complete cure for retinitis pigmentosa is not present. So a treatment protocol has to be adopted that helps in at least the symptomatic relief. In Ayurveda, the signs and symptoms of this can be compared with the Lakshanas of Doshandha which is one among the Dristigata Roga. It is considered as a diseased condition in which sunset will obliterate the Dristi Mandala and makes the person blind at night time. During morning hours the rising sunrays will disperse the accumulated Dosas from Dristi to clear vision. This disease resembles Kaphajatimira in its pathogenesis, but the night blindness is the special feature. Since the disease is purely Kaphaja, a treatment attempt is planned in Kaphara and Brimhana line. The present paper discusses a case of retinitis pigmentosa and it’s Ayurvedic Treatment.

Clinical spectrum, genetic associations and management outcomes of Coats-like exudative retinal vasculopathy in autosomal recessive retinitis pigmentosa

2021 ◽  
pp. 1-8
Author(s):  
Moustafa Magliyah ◽  
Abdulaziz A. Alshamrani ◽  
Patrik Schatz ◽  
Ibrahim Taskintuna ◽  
Yahya Alzahrani ◽  
...  
Keyword(s):  
Retinitis Pigmentosa ◽  
Autosomal Recessive ◽  
Clinical Spectrum ◽  
Genetic Associations

Overproduction of yeast viruslike particles by strains deficient in a mitochondrial nuclease

1989 ◽  
Vol 9 (8) ◽  
pp. 3323-3331
Author(s):  
Y X Liu ◽  
C L Dieckmann
Keyword(s):  
Coat Protein ◽  
Killer Toxin ◽  
Nuclear Gene ◽  
Fold Increase ◽  
Mitochondrial Outer Membrane ◽  
Gene Encoding ◽  
Recessive Mutations ◽  
A Genome ◽  
Nonfermentable Carbon Source ◽  
Viruslike Particles

Saccharomyces cerevisiae strains are often host to several types of cytoplasmic double-stranded RNA (dsRNA) genomes, some of which are encapsidated by the L-A dsRNA product, an 86,000-dalton coat protein. Here we present the finding that nuclear recessive mutations in the NUC1 gene, which encodes the major nonspecific nuclease of yeast mitochondria, resulted in at least a 10-fold increase in amounts of the L-A dsRNA and its encoded coat protein. The effect of nuc1 mutations on L-A abundance was completely suppressed in strains that also hosted the killer-toxin-encoding M dsRNA. Both NUC1 and nuc1 strains containing the L-A genome exhibited an increase in coat protein abundance and a concomitant increase in L-A dsRNA when the cells were grown on a nonfermentable carbon source rather than on glucose, an effect independent of the increase in coat protein due to nuc1 mutations or to the absence of M. The increase in L-A expression in nuc1 strains was similar to that observed in strains with mutations in the nuclear gene encoding the most abundant outer mitochondrial membrane protein, porin. nuc1 mutations did not affect the level of porin in the mitochondrial outer membrane. Since the effect of mutations in nuc1 was to alter the copy number of the L-A coat protein genome rather than to change the level of the M toxin genome (as do mak and ski mutations), these mutations define a new class of nuclear genes affecting yeast dsRNA abundance.

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