Description of Research Expertise
Retinal degeneration, photoreceptor cell death, light-induced retinal damage, retinal remodeling, neuroprotection, gene therapy, optogenetics.
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 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), Jacobson and Cideciyan (Univ. Penn),Hauswirth 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:
Raghavi Sudharsan (Post-doctoral fellow)
Svetlana Savina (Research Specialist)
Inna Martynyuk (Research Specialist)
Kendra McDaid (Animal Research Lab Specialist)
Natalia Dolgova (Research Specialist)
Cecilia Leon (Undergraduate Student)
Beltran,WA, Cideciyan,AV, Guziewicz,KE, Iwabe,S,Swider,M.,Erin M. Scott, Svetlana V. Savina, Gordon Ruthel, Frank Stefano, Lingli Zhang, Richard Zorger, Alexander Sumaroka, Samuel G. Jacobson, Gustavo D. Aguirre Canine retina has a primate fovea-like bouquet of cone photoreceptors which is affected by inherited macular degenerations
PLoS One (in press): , 2014.Genini Sem, Beltran William A, Aguirre Gustavo D Up-regulation of tumor necrosis factor superfamily genes in early phases of photoreceptor degeneration. PloS one 8: e85408, 2013.Guziewicz Karina E, Zangerl Barbara, Komáromy András M, Iwabe Simone, Chiodo Vincent A, Boye Sanford L, Hauswirth William W, Beltran William A, Aguirre Gustavo D Recombinant AAV-mediated BEST1 transfer to the retinal pigment epithelium: analysis of serotype-dependent retinal effects. PloS one 8: e75666, 2013.Cideciyan Artur V, Jacobson Samuel G, Beltran William A, Sumaroka Alexander, Swider Malgorzata, Iwabe Simone, Roman Alejandro J, Olivares Melani B, Schwartz Sharon B, Komáromy András M, Hauswirth William W, Aguirre Gustavo D Human retinal gene therapy for Leber congenital amaurosis shows advancing retinal degeneration despite enduring visual improvement. Proceedings of the National Academy of Sciences of the United States of America 110: E517-25, 2013.Beltran William A, Cideciyan Artur V, Lewin Alfred S, Iwabe Simone, Khanna Hemant, Sumaroka Alexander, Chiodo Vince A, Fajardo Diego S, Román Alejandro J, Deng Wen-Tao, Swider Malgorzata, Alemán Tomas S, Boye Sanford L, Genini Sem, Swaroop Anand, Hauswirth William W, Jacobson Samuel G, Aguirre Gustavo D 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 of the United States of America 109: 2132-7, 2012.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.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.Gu Danian, Beltran William A, Pearce-Kelling Sue, Li Zexiao, Acland Gregory M, Aguirre Gustavo D Steroids do not prevent photoreceptor degeneration in the light-exposed T4R rhodopsin mutant dog retina irrespective of AP-1 inhibition. Investigative ophthalmology & visual science 50: 3482-94, 2009.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.