Brian D. Perkins, Ph.D.
Lerner Research Institute,
9500 Euclid Avenue, Cleveland, Ohio 44195
Phone: (216) 444-9683
Research in the laboratory of Brian D. Perkins, PhD, uses zebrafish and induced pluripotent stem cell (iPSC) models to study photoreceptor degeneration and regeneration.
Inherited retinal diseases lead to irreversible loss of rod and cone photoreceptors and frequently result in blindness. Leber’s Congenital Amaurosis (LCA) is the most common blinding disorder in children. Unfortunately, the body has no way to replace those cells once they are gone. Mutations in the gene for Centrosomal Protein of 290 kDa (CEP290) are one of the leading causes of LCA, as well as other ciliopathies such as Joubert Syndrome (JBTS) and Bardet-Biedl Syndrome (BBS). Importantly, photoreceptor degeneration is one of the most common manifestations in ciliopathies. The long-term goals of this laboratory are to understand the mechanisms regulating the formation of photoreceptor outer segments and to understand how to regenerate photoreceptors in genetic models of retinal degeneration. Our laboratory utilizes a complementary approach of zebrafish mutants in cep290 and several other cilia genes, as well as 3D retinal cups generated from patient-derived human iPSCs. Zebrafish cep290 mutants undergo retinal degeneration and we are exploring the mechanisms that lead to photoreceptor loss and attempting to identify signals that can trigger regeneration in these mutant zebrafish. We are also using iPSCs created from patients with CEP290 mutations to make retinal organoids (also known as “retinas-in-a-dish”) in order to establish the mechanisms that determine disease severity. Our goal is to combine knowledge from stem cell derived retina and zebrafish to develop better therapies for LCA patients in order to restore vision.
The goal of my laboratory is to understand what causes the rods and cones of the retina die in genetic forms of blindness. We use zebrafish as a model to study inherited eye disorders in humans. Specifically, we are investigating zebrafish with mutations in the gene cep290, as mutations in this gene are a major cause of Leber Congenital Amaurosis (LCA), an inherited form of childhood blindness.
- Ramsey, M. and Perkins, B. D. (2013) Basal bodies exhibit polarized positioning in zebrafish cone photoreceptors. Journal of Comparative Neurology. 521(8):1803-16. PMID:23171982
- Wasfy, M. M., Matsui, J. I, Miller, J., Dowling, J. E., and Perkins, B. D. (2014) myosin 7aa-/- mutant zebrafish show photoreceptor degeneration and reduced electroretinographic responses. Experimental Eye Research. 122:65-76. PMCID: PMC4034177
- Krock, B. L., and Perkins, B. D. (2014) The Par-PrkC polarity complex is required for ciliogenesis in vertebrate photoreceptors. PLoS One 9(8) e104661 PMID: 251447.
- DiCicco RM*, Bell BA*, Kaul C, Hollyfield JG, Anand-Apte B, Perkins BD, Tao YK, and Yuan A. (2014) Retinal Regeneration Following OCT-guided Laser Injury in Zebrafish. Invest Ophthalmol Vis Sci. Sep 9;55(10):6281-8. PMID: 25205862.
- Babino, D., Perkins, B. D., Kindermann, A., Oberhauser, V., and von Lintig, J. (2015) The Role of 11-cis-Retinyl Esters in Vertebrate Cone Vision. FASEB J. 2015. 29(1):216-26. PMID: 25326538
- Fogerty, J., Denton, K, and Perkins, B. D. (2016) Mutations in the Dynein1 Complex are Permissible for Basal Body Migration in Photoreceptors but Alter Rab6 Localization. Adv. Exp. Med. Biol. 854:209-15. PMID: 26427413
- Daniele, L. L., Emran, F., Lobo, G. P., Gaivin, R. J., and Perkins, B. D. (2016) Mutation of wrb, a Component of the Guided Entry of Tail-Anchored Protein (GET) Pathway, Disrupts Photoreceptor Synapse Structure and Function. Investigative Ophthalmology and Visual Sciences 57(7):2942-54. PMID: 27273592
- Song, P., Dudinsky, L., Fogerty, J., Gaivin, R. J., and Perkins, B. D. (2016) Arl13b Interacts with Vangl2 to Regulate Cilia and Photoreceptor Outer Segment Length in Zebrafish. Investigative Ophthalmology and Visual Sciences. 2016 Aug 1;57(10):4517-26. PubMed PMID: 27571019; PubMed Central PMCID: PMC5015978.
- Bell, B. A., Yuan, A., Dicicco, R. M., Fogerty, J., Lessieur, E. M., and Perkins B. D. (2016) The Adult Zebrafish Retina: In vivo Optical Sectioning with Confocal Scanning Laser Ophthalmoscopy and Spectral-Domain Optical Coherence Tomography. Experimental Eye Research. Dec. 153:65-78 PubMed PMID: 27720860 PubMed Central PMCID: PMC5120996
- Lessieur, E. M., Fogerty, J., Gaivin, R. J., Song P., and Perkins, B. D. (2017) The ciliopathy gene ahi1 is required for zebrafish cone photoreceptor outer segment morphogenesis. Investigative Ophthalmology and Visual Sciences. Jan 1;58(1):448-460. PubMed PMID: 28118669; PubMed Central PMCID: PMC5270624.
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