Description of Research Expertise
Retinal degeneration, photoreceptor cell death, light-induced retinal damage, retinal remodeling, neuroprotection, gene therapy.
Keywords: Retinal degeneration, X-linked RP, RPGR, autosomal dominant RP, rhodopsin, light damage, CNTF.
Inherited retinal degenerations constitute a major cause of blindness in dogs and humans worldwide, and share a common feature: the degeneration and death of the photoreceptor cells. Although a significant number of genes associated with retinitis pigmentosa (RP) have been identified, there is currently no treatment available.
Dr. Beltran’s research is focused at examining the cellular and molecular mechanisms of photoreceptor death in canine models of retinal degeneration, and developing novel therapeutic approaches aimed at curing or slowing the progression of this group of diseases in dogs and human patients.
Studies currently conducted in Dr. Beltran’s laboratory include:
1) Investigating the signaling pathways of cell death in canine models of X-linked RP caused by mutations in the RPGR gene.
2) Elucidating the pathogenesis of light-induced retinal degeneration in the T4R rhodopsin mutant dog, a model of human autosomal dominant RP.
3) Testing neuroprotective agents such as ciliary neurotrophic factor (CNTF) for their potential photoreceptor rescue properties.
4) Developing and testing corrective gene therapy approaches for RPGR-XLRP, and RHO-ADRP in collaboration with the Aguirre (Univ. Penn), Hauswirth (Univ. Florida), Jacobson (Univ. Penn), and Lewin (Univ. Florida) laboratories.
5) Testing optogenetic tools as a potential strategy for recovering visual function in patients with late stages of retinal degeneration.
Current Lab Members:
Stefania Marsili (Post-doctoral fellow)
Svetlana Savina (Research Specialist)
Kendra McDaid (Research Specialist
Natalie Boursiquot (Veterinary student)
William A. Beltran, Artur V. Cideciyan, Alfred S. Lewin, Simone Iwabe,Hemant Khanna, Alexander Sumaroka,Vince A. Chiodo, Diego S. Fajardo, Alejandro J. Román, Wen-Tao Deng, Malgorzata Swider, Tomas S. Alemán,Sanford L. Boye, Sem Genini, Anand Swaroo, William W. Hauswirth, Samuel G. Jacobson,and Gustavo D. Aguirre Gene therapy rescues photoreceptor blindness in dogs
and paves the way for treating human X-linked
retinitis pigmentosa Proceedings of the National Academy of Sciences, USA 109: 2132-2137, 2012.Berta Ágnes I, Boesze-Battaglia Kathleen, Genini Sem, Goldstein Orly, O'Brien Paul J, Szél Ágoston, Acland Gregory M, Beltran William A, Aguirre Gustavo D Photoreceptor cell death, proliferation and formation of hybrid rod/S-cone photoreceptors in the degenerating STK38L mutant retina. PloS one 6: e24074, 2011.Beltran W A, Boye S L, Boye S E, Chiodo V A, Lewin A S, Hauswirth W W, Aguirre G D rAAV2/5 gene-targeting to rods:dose-dependent efficiency and complications associated with different promoters. Gene therapy 17: 1162-74, 2010.Genini Sem, Zangerl Barbara, Slavik Julianna, Acland Gregory M, Beltran William A, Aguirre Gustavo D Transcriptional profile analysis of RPGRORF15 frameshift mutation identifies novel genes associated with retinal degeneration. Investigative ophthalmology & visual science 51: 6038-50, 2010.Beltran WA, Acland GM, Aguirre GD Age-dependent disease expression determines remodeling of the retinal mosaic in carriers of RPGR exon ORF15 mutations. Investigative Ophthalmology and Visual Sciences 50: 3985-3995, 2009.Beltran WA The use of canine models of retinal degeneration to test novel therapeutic approaches. Veterinary Ophthalmology 12: 192-204, 2009.Gu D, Beltran WA, Pearce-Kelling S, Li Z, Acland GM, Aguirre GD, Steroids do not prevent photoreceptor degeneration in the light exposed T4R Rhodopsin dog retina irrespective of AP-1 inhibition. Investigative Ophthalmology & Visual Sciences 50: 3482-3494, 2009.Gu D., Beltran W. A., Li Z., Acland G.M., Aguirre G.D. Clinical light exposure, photoreceptor degeneration and AP-1 activation: a cell death or cell survival signal in the rhodopsin mutant retina? Investigative Ophthalmology and Visual Sciences 48(11): 4907-4918, 2007.Beltran, W. A., Wen, R., Acland, G. M., Aguirre, G. D. Intravitreal injection of ciliary neurotrophic factor (CNTF) causes peripheral remodeling and does not prevent photoreceptor loss in canine RPGR mutant retina. Experimental Eye Research 84: 753-71, 2007.Beltran, W. A. Hammond, P. Acland, G. M. Aguirre, G. D. A frameshift mutation in RPGR exon ORF15 causes photoreceptor degeneration and inner retina remodeling in a model of X-linked retinitis pigmentosa. Investigative Ophthalmology & Visual Science 47: 1669-81, 2006.
DVM (Veterinary Medicine) National Veterinary College of Alfort, FRANCE, 1994Master (Biological and Medical Sciences) University of Paris, School of Medicine, Kremlin-Bicetre, FRANCE, 1997PhD (Comparative Biomedical Sciences) Cornell University, Ithaca, NY, USA, 2006