Inherited retinal dystrophy: primary defect in pigment epithelium determined with experimental rat chimeras

Science ◽  
1976 ◽  
Vol 192 (4241) ◽  
pp. 799-801 ◽  
Author(s):  
R. Mullen ◽  
M. LaVail
Keyword(s):  
Pigment Epithelium ◽  
Retinal Dystrophy ◽  
Primary Defect ◽  
Inherited Retinal Dystrophy

scholarly journals THE ROLE OF THE PIGMENT EPITHELIUM IN THE ETIOLOGY OF INHERITED RETINAL DYSTROPHY IN THE RAT

1971 ◽  
Vol 49 (3) ◽  
pp. 664-682 ◽  
Author(s):  
Dean Bok ◽  
Michael O. Hall
Keyword(s):  
Cell Death ◽  
Outer Segment ◽  
Pigment Epithelium ◽  
Retinal Dystrophy ◽  
Visual Cell ◽  
Sprague Dawley ◽  
Inherited Retinal Dystrophy ◽  
Rcs Rats ◽  
Electron Microscopes ◽  
And Control

Visual cell outer segment renewal was studied in eyes of mutant Royal College of Surgeons (RCS) and Sprague-Dawley (control) rats by a combination of microscopy and radioautography with the light and electron microscopes. RCS and control rats were injected with amino acids-3H at 11 days of age. Radioactive rod outer segment discs were assembled at the outer segment base from radioactive proteins synthesized in the rod inner segments. In controls, all radioactive discs assembled at 11 days of age were displaced the length of the outer segments, removed from outer segment tips, and phagocytized by the pigment epithelium by 8 days after injection. In the RCS rats, disc assembly and displacement resembled controls for the first 3 days after injection. However, as disc assembly continued for some time thereafter, a layer of labeled, disorganized, lamellar debris accumulated between the outer segment tips and the pigment epithelium. The buildup of debris was accompanied by visual cell death. At no time during the study was there evidence for phagocytic activity by the pigment epithelium. 61 days after injection, the layer of debris was the only heavily radioactive component in the retina. In the retina of RCS rats, the outer segment renewal mechanism malfunctions because the pigment epithelium does not fulfill its normal phagocytic role. The end result is visual cell death and blindness.

Inherited retinal dystrophy in RCS rats: a deficiency in vitamin A esterification in pigment epithelium

Nature ◽  
1981 ◽  
Vol 293 (5829) ◽  
pp. 217-220 ◽  
Author(s):  
E. R. Berman ◽  
N. Segal ◽  
S. Photiou ◽  
H. Rothman ◽  
L. Feeney-Burns
Keyword(s):  
Vitamin A ◽  
Pigment Epithelium ◽  
Retinal Dystrophy ◽  
Inherited Retinal Dystrophy ◽  
Rcs Rats

Chronic untreated retinal detachment in a patient with choroideremia provides insight into the disease process and potential therapy

2021 ◽  
pp. 112067212199472
Author(s):  
Maria Pilar Martin-Gutierrez ◽  
Thomas MW Buckley ◽  
Robert E MacLaren
Keyword(s):  
Gene Therapy ◽  
Retinal Detachment ◽  
Rhegmatogenous Retinal Detachment ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Retinal Dystrophy ◽  
Disease Process ◽  
Peripheral Retina ◽  
Inherited Retinal Dystrophy ◽  
Insight Into

Aim: We present the case of a 72-year-old male with advanced choroideremia and a left chronic rhegmatogenous retinal detachment, which to our knowledge is the first formal report of a retinal detachment in this disease. Background: Choroideremia is a rare X-linked inherited retinal dystrophy, caused by mutations in the CHM gene which encodes Rab escort protein 1 (REP1), and affected males typically experience a progressive centripetal loss of vision. The disease pathology is caused by a primary retinal pigment epithelium degeneration, which leads to secondary loss of photoreceptors and choriocapillaris. This in turn leads to fusion of the degenerate outer retinal layers resulting in a retinopexy that is known to make subretinal gene therapy particularly challenging in these patients. Conclusion: Although retinal gene therapy is commonly targeted to the macular area in choroideremia, the observation of a rhegmatogenous retinal detachment indicates that the peripheral retina may not fuse with the residual choroid as occurs in the equatorial and macular regions. If this hypothesis is correct, targeting gene therapy to the retinal periphery even in advanced cases may be feasible and could potentially be used to preserve navigational vision.

Na-K-activated adenosinetriphosphatase in retinae of rats with and without inherited retinal dystrophy

1970 ◽  
Vol 10 (5) ◽  
pp. 435-438 ◽  
Author(s):  
F.J.M. Daemen ◽  
J.J.H.H.M. de Pont ◽  
F. Lion ◽  
S.L. Bonting
Keyword(s):  
Retinal Dystrophy ◽  
Inherited Retinal Dystrophy

scholarly journals INHERITED RETINAL DYSTROPHY IN THE RAT

1962 ◽  
Vol 14 (1) ◽  
pp. 73-109 ◽  
Author(s):  
John E. Dowling ◽  
Richard L. Sidman
Keyword(s):  
Pigment Epithelium ◽  
Light And Electron Microscopy ◽  
Retinal Dystrophy ◽  
Photoreceptor Cells ◽  
Pigment Cells ◽  
Membrane Thickness ◽  
Outer Segments ◽  
Progressive Loss ◽  
Retinal Rods ◽  
Microscopy Data

Retinal dystrophies, known in man, dog, mouse, and rat, involve progressive loss of photoreceptor cells with onset during or soon after the developmental period. Functional (electroretinogram), chemical (rhodopsin analyses) and morphological (light and electron microscopy) data obtained in the rat indicated two main processes: (a) overproduction of rhodopsin and an associated abnormal lamellar tissue component, (b) progressive loss of photoreceptor cells. The first abnormality recognized was the appearance of swirling sheets or bundles of extracellular lamellae between normally developing retinal rods and pigment epithelium; membrane thickness and spacing resembled that in normal outer segments. Rhodopsin content reached twice normal values, was present in both rods and extracellular lamellae, and was qualitatively normal, judged by absorption maximum and products of bleaching. Photoreceptors attained virtually adult form and ERG function. Then rod inner segments and nuclei began degenerating; the ERG lost sensitivity and showed selective depression of the a-wave at high luminances. Outer segments and lamellae gradually degenerated and rhodopsin content decreased. No phagocytosis was seen, though pigment cells partially dedifferentiated and many migrated through the outer segment-debris zone toward the retina. Eventually photoreceptor cells and the b-wave of the ERG entirely disappeared. Rats kept in darkness retained electrical activity, rhodopsin content, rod structure, and extracellular lamellae longer than litter mates in light.

scholarly journals Innate and Autoimmunity in the Pathogenesis of Inherited Retinal Dystrophy

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 630 ◽  
Author(s):  
T. J. Hollingsworth ◽  
Alecia K. Gross
Keyword(s):  
Disease Progression ◽  
Age Of Onset ◽  
Retinal Dystrophy ◽  
Inherited Retinal Dystrophies ◽  
Retinal Dystrophies ◽  
Major Player ◽  
Inherited Retinal Dystrophy ◽  
Rate Of Progression ◽  
Immunohistochemical Methods ◽  
Onset Rate

Inherited retinal dystrophies (RDs) are heterogenous in many aspects including genes involved, age of onset, rate of progression, and treatments. While RDs are caused by a plethora of different mutations, all result in the same outcome of blindness. While treatments, both gene therapy-based and drug-based, have been developed to slow or halt disease progression and prevent further blindness, only a small handful of the forms of RDs have treatments available, which are primarily for recessively inherited forms. Using immunohistochemical methods coupled with electroretinography, optical coherence tomography, and fluorescein angiography, we show that in rhodopsin mutant mice, the involvement of both the innate and the autoimmune systems could be a strong contributing factor in disease progression and pathogenesis. Herein, we show that monocytic phagocytosis and inflammatory cytokine release along with protein citrullination, a major player in forms of autoimmunity, work to enhance the progression of RD associated with a rhodopsin mutation.

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