Tyrosine hydroxylase-positive amacrine interneurons in the mouse retina are resistant against the application of various parkinsonian toxins

Abstract

Toxins such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 6-hydroxydopamine (6-OHDA), or rotenone have been used to induce degeneration of dopaminergic (DA) neurons in the nigrostriatal pathway and to reproduce pathological characteristics of Parkinson's disease (PD). DA neurons are also present in the retina, and visual impairments in PD patients have been reported. We examined the vulnerability of TH-positive (TH +) amacrine interneurons in the retina against MPTP, 6-OHDA, or rotenone-induced cell death. We intraperitoneally (i.p.) injected mice with MPTP, which induced degeneration of DA neurons in the midbrain. However, no death of TH + amacrine cells was detectable in the same mice. HPLC analysis revealed a 9 times lower level of the toxic metabolite of MPTP, MPP +, in the eye compared with the striatum. Another membrane-permeable compound (Tat-Hsp70) could be delivered into the retina after i.p. application, suggesting that the blood–retina barrier (BRB) could be overcome after systemic application. Possible reason for the survival of retinal amacrine cells after systemic MPTP application was a less efficient conversion into toxic MPP + in the retina or a general higher resistance against toxic insults of retinal DA neurons compared with DA neurons in the substantia nigra pars compacta (SN pc). Therefore, we directly injected high doses of MPP +, 6-OHDA, or rotenone into the eye. No loss of TH + amacrine cells in the retina was observed, suggesting different properties and less vulnerability of amacrine neurons compared with DA neurons in the midbrain.