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Human retinal disease from AIPL1 gene mutations: foveal cone loss with minimal macular photoreceptors and rod function remaining.
Invest Ophthalmol Vis Sci. 2011 Jan 05; 52(1):70-9.IO

Abstract

PURPOSE

To determine the human retinal phenotype caused by mutations in the gene encoding AIPL1 (Aryl hydrocarbon receptor-interacting protein-like 1) now that there are proof-of-concept results for gene therapy success in Aipl1-deficient mice.

METHODS

Leber congenital amaurosis (LCA) patients (n = 10) and one patient with a later-onset retinal degeneration (RD) and AIPL1 mutations were studied by ocular examination, retinal imaging, perimetry, full-field sensitivity testing, and pupillometry.

RESULTS

The LCA patients had severe visual acuity loss early in life, nondetectable electroretinograms (ERGs), and little or no detectable visual fields. Hallmarks of retinal degeneration were present in a wide region, including the macula and midperiphery; there was some apparent peripheral retinal sparing. Cross-sectional imaging showed foveal cone photoreceptor loss with a ring of minimally preserved paracentral photoreceptor nuclear layer. Features of retinal remodeling were present eccentric to the region of detectable photoreceptors. Full-field sensitivity was reduced by at least 2 log units, and chromatic stimuli, by psychophysics and pupillometry, revealed retained but impaired rod function. The RD patient, examined serially over two decades (ages, 45-67 years), retained an ERG in the fifth decade of life with abnormal rod and cone signals; and there was progressive loss of central and peripheral function.

CONCLUSIONS

AIPL1-LCA, unlike some other forms of LCA with equally severe visual disturbance, shows profound loss of foveal as well as extrafoveal photoreceptors. The more unusual late-onset and slower form of AIPL1 disease may be better suited to gene augmentation therapy and is worthy of detection and further study.

Authors+Show Affiliations

Department of Ophthalmology, University of Pennsylvania, Philadelphia, PA, USA. jacobsos@mail.med.upenn.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20702822

Citation

Jacobson, Samuel G., et al. "Human Retinal Disease From AIPL1 Gene Mutations: Foveal Cone Loss With Minimal Macular Photoreceptors and Rod Function Remaining." Investigative Ophthalmology & Visual Science, vol. 52, no. 1, 2011, pp. 70-9.
Jacobson SG, Cideciyan AV, Aleman TS, et al. Human retinal disease from AIPL1 gene mutations: foveal cone loss with minimal macular photoreceptors and rod function remaining. Invest Ophthalmol Vis Sci. 2011;52(1):70-9.
Jacobson, S. G., Cideciyan, A. V., Aleman, T. S., Sumaroka, A., Roman, A. J., Swider, M., Schwartz, S. B., Banin, E., & Stone, E. M. (2011). Human retinal disease from AIPL1 gene mutations: foveal cone loss with minimal macular photoreceptors and rod function remaining. Investigative Ophthalmology & Visual Science, 52(1), 70-9. https://doi.org/10.1167/iovs.10-6127
Jacobson SG, et al. Human Retinal Disease From AIPL1 Gene Mutations: Foveal Cone Loss With Minimal Macular Photoreceptors and Rod Function Remaining. Invest Ophthalmol Vis Sci. 2011 Jan 5;52(1):70-9. PubMed PMID: 20702822.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Human retinal disease from AIPL1 gene mutations: foveal cone loss with minimal macular photoreceptors and rod function remaining. AU - Jacobson,Samuel G, AU - Cideciyan,Artur V, AU - Aleman,Tomas S, AU - Sumaroka,Alexander, AU - Roman,Alejandro J, AU - Swider,Malgorzata, AU - Schwartz,Sharon B, AU - Banin,Eyal, AU - Stone,Edwin M, Y1 - 2011/01/05/ PY - 2010/8/13/entrez PY - 2010/8/13/pubmed PY - 2011/2/8/medline SP - 70 EP - 9 JF - Investigative ophthalmology & visual science JO - Invest. Ophthalmol. Vis. Sci. VL - 52 IS - 1 N2 - PURPOSE: To determine the human retinal phenotype caused by mutations in the gene encoding AIPL1 (Aryl hydrocarbon receptor-interacting protein-like 1) now that there are proof-of-concept results for gene therapy success in Aipl1-deficient mice. METHODS: Leber congenital amaurosis (LCA) patients (n = 10) and one patient with a later-onset retinal degeneration (RD) and AIPL1 mutations were studied by ocular examination, retinal imaging, perimetry, full-field sensitivity testing, and pupillometry. RESULTS: The LCA patients had severe visual acuity loss early in life, nondetectable electroretinograms (ERGs), and little or no detectable visual fields. Hallmarks of retinal degeneration were present in a wide region, including the macula and midperiphery; there was some apparent peripheral retinal sparing. Cross-sectional imaging showed foveal cone photoreceptor loss with a ring of minimally preserved paracentral photoreceptor nuclear layer. Features of retinal remodeling were present eccentric to the region of detectable photoreceptors. Full-field sensitivity was reduced by at least 2 log units, and chromatic stimuli, by psychophysics and pupillometry, revealed retained but impaired rod function. The RD patient, examined serially over two decades (ages, 45-67 years), retained an ERG in the fifth decade of life with abnormal rod and cone signals; and there was progressive loss of central and peripheral function. CONCLUSIONS: AIPL1-LCA, unlike some other forms of LCA with equally severe visual disturbance, shows profound loss of foveal as well as extrafoveal photoreceptors. The more unusual late-onset and slower form of AIPL1 disease may be better suited to gene augmentation therapy and is worthy of detection and further study. SN - 1552-5783 UR - https://www.unboundmedicine.com/medline/citation/20702822/Human_retinal_disease_from_AIPL1_gene_mutations:_foveal_cone_loss_with_minimal_macular_photoreceptors_and_rod_function_remaining_ L2 - http://iovs.arvojournals.org/article.aspx?doi=10.1167/iovs.10-6127 DB - PRIME DP - Unbound Medicine ER -