RPGR-Associated Retinal Degeneration in Human X-Linked RP and a Murine Model
| Autor: | Alejandro J. Roman, Peter Bell, Dina Y. Gewaily, Artur V. Cideciyan, Maria P. Limberis, Samuel G. Jacobson, Alan F. Wright, Anand Swaroop, Sharon B. Schwartz, Forbes D C Manson, Wei Chieh Huang, Sam Sadigh, James M. Wilson |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Retinal degeneration
Adult Male endocrine system medicine.medical_specialty genetic structures Adolescent Visual Acuity Biology medicine.disease_cause chemistry.chemical_compound Mice Young Adult Retinal Rod Photoreceptor Cells Ophthalmology Retinitis pigmentosa Conditional gene knockout medicine Animals Humans Child Eye Proteins X-linked recessive inheritance Aged Mice Knockout Mutation Retina Retinal Degeneration Retinal Genetic Diseases X-Linked Retinitis pigmentosa GTPase regulator Articles Middle Aged medicine.disease eye diseases Disease Models Animal medicine.anatomical_structure chemistry Child Preschool Cancer research Retinal Cone Photoreceptor Cells Female sense organs Retinitis Pigmentosa |
| Zdroj: | Huang, W C, Wright, A F, Roman, A J, Cideciyan, A V, Manson, F D, Gewaily, D Y, Schwartz, S B, Sadigh, S, Limberis, M P, Bell, P, Wilson, J M, Swaroop, A & Jacobson, S G 2012, ' RPGR-associated retinal degeneration in human X-linked RP and a murine model ', Investigative Ophthalmology & Visual Science, vol. 53, no. 9, pp. 5594-608 . https://doi.org/10.1167/iovs.12-10070 |
| DOI: | 10.1167/iovs.12-10070 |
| Popis: | PURPOSE: We investigated the retinal disease due to mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene in human patients and in an Rpgr conditional knockout (cko) mouse model.METHODS: XLRP patients with RPGR-ORF15 mutations (n = 35, ages at first visit 5-72 years) had clinical examinations, and rod and cone perimetry. Rpgr-cko mice, in which the proximal promoter and first exon were deleted ubiquitously, were back-crossed onto a BALB/c background, and studied with optical coherence tomography and electroretinography (ERG). Retinal histopathology was performed on a subset.RESULTS: Different patterns of rod and cone dysfunction were present in patients. Frequently, there were midperipheral losses with residual rod and cone function in central and peripheral retina. Longitudinal data indicated that central rod loss preceded peripheral rod losses. Central cone-only vision with no peripheral function was a late stage. Less commonly, patients had central rod and cone dysfunction, but preserved, albeit abnormal, midperipheral rod and cone vision. Rpgr-cko mice had progressive retinal degeneration detectable in the first months of life. ERGs indicated relatively equal rod and cone disease. At late stages, there was greater inferior versus superior retinal degeneration. CONCLUSIONS: RPGR mutations lead to progressive loss of rod and cone vision, but show different patterns of residual photoreceptor disease expression. Knowledge of the patterns should guide treatment strategies. Rpgr-cko mice had onset of degeneration at relatively young ages and progressive photoreceptor disease. The natural history in this model will permit preclinical proof-of-concept studies to be designed and such studies should advance progress toward human therapy. |
| Databáze: | OpenAIRE |
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