A comparison of the effects of kainic acid on somatostatin, substance P and dopamine in the rabbit retina

Abstract

Groups of adult, male Dutch belted rabbits received intravitreal injections of varying doses (30-240 nmol) of the excitatory neurotoxin kainic acid (KA) into one eye and saline vehicle into the other. One week later a segment of each retina was examined histologically and the remainder was assayed for somatostatin-like immunoreactivity (SLI), substance P-like immunoreactivity (SPLI), dopamine (DA) and protein. Histologically, KA at doses of 120 and 240 nmol produced destruction of the inner layers of the retina, with preservation of the photoreceptors. This damage is correlated with a dose-related depletion of retinal protein content. At KA doses of 120 and 240 nmol, both SPLI and DA content were reduced to 5-10% of control values. Although KA significantly reduced the retinal content of SLI even at a dose of 30 nmol, the greatest mean depletion of SLI observed at any dose was 50%. This failure of KA to reduce retinal SLI content by more than 50% at doses of KA which produce severe histologic damage to the neural retina and dramatic depletions of SPLI and DA content demonstrates that the SLI-containing structures of the rabbit retina are partially resistant to the neurotoxic action of KA. We hypothesize that SLI in the rabbit retina is contained in two pharmacologic types of cells in about equal abundance; one type is sensitive to and one type resistant to KA. In contrast, substance P- and dopamine-containing retinal neurons are uniformly sensitive to destruction by KA.