Purpose: The development of new approaches to human vision restoration could be greatly accelerated with the use of nonhuman primate models; however, there is a paucity of primate models of outer retina degeneration with good spatial localization. To limit ablation to the photoreceptors, we developed a new approach that uses a near-infrared ultrafast laser, focused using adaptive optics, to concentrate light in a small focal volume within the retina. Methods: In the eyes of eight anesthetized macaques, 187 locations were exposed to laser powers from 50 to 210 mW. Laser exposure locations were monitored for up to 18 months using fluorescein angiography (FA), optical coherence tomography (OCT), scanning laser ophthalmoscopy (SLO), adaptive optics scanning laser ophthalmoscope (AOSLO) reflectance imaging, two-photon excited fluorescence (TPEF) ophthalmoscopy, histology, and calcium responses of retinal ganglion cells. Results: This method produced localized photoreceptor loss with minimal axial spread of damage to other retinal layers, verified by in-vivo structural imaging and histologic examination, although in some cases evidence of altered autofluorescence was found in the adjacent retinal pigment epithelium (RPE). Functional assessment using blood flow imaging of the retinal plexus and calcium imaging of the response of ganglion cells above the photoreceptor loss shows that inner retinal circuitry was preserved. Conclusions: Although different from a genetic model of retinal degeneration, this model of localized photoreceptor loss may provide a useful testbed for vision restoration studies in nonhuman primates. Translational Relevance: With this model, a variety of vision restoration methods can be tested in the non-human primate. Copyright 2020 The Authors.
Purpose: The development of new approaches to human vision restoration could be greatly accelerated with the use of nonhuman primate models; however, there is a paucity of primate models of outer retina degeneration with good spatial localization. To limit ablation to the photoreceptors, we developed a new approach that uses a near-infrared ultrafast laser, focused using adaptive optics, to concentrate light in a small focal volume within the retina. Methods: In the eyes of eight anesthetized macaques, 187 locations were exposed to laser powers from 50 to 210 mW. Laser exposure locations were monitored for up to 18 months using fluorescein angiography (FA), optical coherence tomography (OCT), scanning laser ophthalmoscopy (SLO), adaptive optics scanning laser ophthalmoscope (AOSLO) reflectance imaging, two-photon excited fluorescence (TPEF) ophthalmoscopy, histology, and calcium responses of retinal ganglion cells. Results: This method produced localized photoreceptor loss with minimal axial spread of damage to other retinal layers, verified by in-vivo structural imaging and histologic examination, although in some cases evidence of altered autofluorescence was found in the adjacent retinal pigment epithelium (RPE). Functional assessment using blood flow imaging of the retinal plexus and calcium imaging of the response of ganglion cells above the photoreceptor loss shows that inner retinal circuitry was preserved. Conclusions: Although different from a genetic model of retinal degeneration, this model of localized photoreceptor loss may provide a useful testbed for vision restoration studies in nonhuman primates. Translational Relevance: With this model, a variety of vision restoration methods can be tested in the non-human primate. Copyright 2020 The Authors.
Authors: M Joseph Phillips; Kyle A Wallace; Sarah J Dickerson; Michael J Miller; Amelia D Verhoeven; Jessica M Martin; Lynda S Wright; Wei Shen; Elizabeth E Capowski; E Ferda Percin; Enio T Perez; Xiufeng Zhong; Maria V Canto-Soler; David M Gamm Journal: Invest Ophthalmol Vis Sci Date: 2012-04-18 Impact factor: 4.799
Authors: M Mehdi Doroudchi; Kenneth P Greenberg; Jianwen Liu; Kimberly A Silka; Edward S Boyden; Jennifer A Lockridge; A Cyrus Arman; Ramesh Janani; Shannon E Boye; Sanford L Boye; Gabriel M Gordon; Benjamin C Matteo; Alapakkam P Sampath; William W Hauswirth; Alan Horsager Journal: Mol Ther Date: 2011-04-19 Impact factor: 11.454
Authors: Ala Moshiri; Rui Chen; Soohyun Kim; R Alan Harris; Yumei Li; Muthuswamy Raveendran; Sarah Davis; Qingnan Liang; Ori Pomerantz; Jun Wang; Laura Garzel; Ashley Cameron; Glenn Yiu; J Timothy Stout; Yijun Huang; Christopher J Murphy; Jeffrey Roberts; Kota N Gopalakrishna; Kimberly Boyd; Nikolai O Artemyev; Jeffrey Rogers; Sara M Thomasy Journal: J Clin Invest Date: 2019-01-22 Impact factor: 14.808
Authors: Juliette E McGregor; Karteek Kunala; Zhengyang Xu; Peter J Murphy; Tyler Godat; Jennifer M Strazzeri; Brittany A Bateman; William S Fischer; Keith Parkins; Colin J Chu; Teresa Puthussery; David R Williams; William H Merigan Journal: Mol Ther Date: 2021-09-20 Impact factor: 11.454