ATP-Induced Photoreceptor Death in a Feline Model of Retinal Degeneration

Abstract

Development of an ATP-induced feline model of retinal degeneration provides a rapid and effective large-eyed animal model for research into vision restoration.

Stimulation of a Suprachoroidal Retinal Prosthesis Drives Cortical Responses in a Feline Model of Retinal Degeneration

“…One eye was injected with a 200-lL solution of sterile phosphate-buffered saline (PBS; 0.9%) containing 0.2 M ATP hydrate to induce photoreceptor degeneration (Sigma Pharmaceuticals Ltd., Melbourne, VIC, Australia) and 0.2 mg dexamethasone to reduce inflammation (4 mg/mL dexamethasone; Aspen Australia, Sydney, NSW, Australia). As sham injections carried a slight risk of cataract formation and a comparison of sham injected and uninjected controls had previously found no differences, 22 the fellow eye was the uninjected control.…”

“…All four animals were a subset of a larger cohort (n ¼ 19) required for another study 22 Unilateral retinal degeneration was induced in all four animals by using a single intravitreal injection of ATP at a concentration of 11 mM at the retina as previously described. 22,24,25 We have previously found that ATP injection induces a global retinal degeneration with a variable pattern of photoreceptor loss, where the most severely affected inner retina occurs in regions containing fewer residual photoreceptor nuclei. 22,23 Briefly, the procedure was performed under anesthesia induced through a subcutaneous injection of ketamine (20 mg/kg; Ilium Ketamil; Troy Laboratories Pty.…”

“…22,24,25 We have previously found that ATP injection induces a global retinal degeneration with a variable pattern of photoreceptor loss, where the most severely affected inner retina occurs in regions containing fewer residual photoreceptor nuclei. 22,23 Briefly, the procedure was performed under anesthesia induced through a subcutaneous injection of ketamine (20 mg/kg; Ilium Ketamil; Troy Laboratories Pty. Ltd., Glendenning, NSW, Australia) and xylazine (2 mg/kg; Ilium Xylazil-20; Troy Laboratories).…”

“…Function was assessed using full-field, twin-flash ERG (Espion; Diagnosys LLC, Lowell, MA, USA) to separate the rod-and cone-pathway-mediated functions. All assessment and analysis methodologies performed in these animals have been described previously 22 and are similar to techniques used in other retinal prosthesis studies.…”

“…22,23 This model provides a unique opportunity to directly compare the effects of suprachoroidal stimulation in a degenerated retina with that in a normally sighted fellow eye within the same animal. The central aim of this study was to examine how loss of photoreceptors and associated retinal remodeling influences the efficacy of suprachoroidal retinal stimulation.…”