Vulnerability of Dopaminergic Amacrine Cells to Chronic Ischemia in a Mouse Model of Oxygen-Induced Retinopathy.
Retinal dopamine deficiency is a potential cause of myopia and visual deficits in retinopathy of prematurity (ROP). We investigated the cellular mechanisms responsible for lowered levels of retinal dopamine in an oxygen-induced retinopathy (OIR) mouse model of ROP.



Retinopathy was induced by exposing mice to 75% oxygen from postnatal day 7 (P7) to P12. Oxygen-induced retinopathy and age-matched control mice were euthanized at P12, P17, P25, or P42 to P50. Immunohistochemistry, electrophysiology, and biochemical approaches were used to determine the effect of OIR on the structure and function of dopaminergic amacrine cells (DACs).



The total number of DACs was unchanged in OIR retinas at P12 despite significant capillary dropout in the central retina. However, a significant loss of DACs was observed in P17 OIR retinas (in which neovascularization was maximal), with the cell loss being more profound in the central (avascular) than in the peripheral (neovascular) regions. Cell loss was persistent in both regions at P25, at which time retinal neovascularization had regressed. At P42, the percentage of DACs lost (54%) was comparable to the percent decrease in total dopamine content (53%). Additionally, it was found that DACs recorded in OIR retinas at P42 to P50 had a complete dendritic field and exhibited relatively normal spontaneous and light-induced electrical activity.



The results suggest that remaining DACs are structurally and functionally intact and that loss of DACs is primarily responsible for the decreased levels of retinal dopamine observed after OIR.
Eye Research Institute Oakland University, Rochester, Michigan, United States.
Nathan J
NJ
Spix
Eye Research Institute Oakland University, Rochester, Michigan, United States.
Lei-Lei
LL
Liu
Ruiz Department of Ophthalmology and Visual Science, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Texas, United States.
Zhijing
Z
Zhang
Eye Research Institute Oakland University, Rochester, Michigan, United States.
Joshua P
JP
Hohlbein
Eye Research Institute Oakland University, Rochester, Michigan, United States.
Cameron L
CL
Prigge
Eye Research Institute Oakland University, Rochester, Michigan, United States.
Shravan
S
Chintala
Ruiz Department of Ophthalmology and Visual Science, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Texas, United States 3Graduate School of Biomedical Sciences, The University of Texas Health Science Center at.
Christophe P
CP
Ribelayga
Eye Research Institute Oakland University, Rochester, Michigan, United States.
Dao-Qi
DQ
Zhang
D025042:Amacrine Cells / Q000473:pathology* / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D007150:Immunohistochemistry; D007511:Ischemia / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D010100:Oxygen / Q000494:pharmacology; D012160:Retina / Q000503:physiopathology; D015861:Retinal Neovascularization / Q000503:physiopathology*; D012171:Retinal Vessels / Q000503:physiopathology; D012178:Retinopathy of Prematurity / Q000503:physiopathology
D010100:Oxygen; D004298:Dopamine