Glaucoma, Starburst amacrine cell, Rat, Acetylcholine, Retinal ganglion cell, Neuroprotection
Acetylcholine (ACh) release by starburst amacrine cells (SACs) has been implicated in the production of retinal waves during early retinal development. Inhibitory gamma-aminobutyric acid (GABA) release by SACs is known to be involved in directional selectivity in the mature retina. However, the role of SAC release of ACh in the adult developed mammalian retina is not entirely understood. Some evidence suggests a neuroprotective effect on retinal ganglion cells (RGCs) acting through alpha7 nicotinic acetylcholine receptors (nAChRs) present in RGCs. If ACh released by SACs is neuroprotective to RGCs, it would follow that this cholinergic transmission might be compromised in glaucoma conditions, at a time point prior to RGC loss. In this study, hypertonic saline injections into the episcleral veins surrounding the eyes of adult Long Evans rats were used to induce glaucoma-like conditions. The effect of this rat glaucoma model on starburst amacrine cell populations was examined at various time points post-insult. Additionally, ACh content within the retina and the expression of nAChRs within the retina were analyzed. It was found that starburst amacrine cell numbers, ACh content, and alpha7 nAChR expression all began to decrease one week after the procedure to induce glaucoma-like conditions, preceding the significant loss of RGCs that typically occurs one month after the same procedure. In pharmacological studies, DMP-543 and Donepezil were used to enhance the effect of ACh at the amacrine cell-RGC synapse. Each of these agents increased RGC survival in the induced glaucoma model. The results obtained from this study support the hypothesis that SACs mediate cholinergic neuroprotection for RGCs. This indicates a potentially novel role of ACh released from SACs in the mature mammalian retina.
Cooley-Themm, C. A., Ameel, Q., Linn, D. M., & Linn, C. L. (2017). Loss of Displaced Starburst Amacrine Cells in a Rat Glaucoma Model. Journal of Ophthalmic Research and Ocular Care, 1(1), Article 1. http://dx.doi.org/10.36959/936/564
Cooley-Themm, C A.; Ameel, Q; Linn, David M.; and Linn, Cindy L., "Loss of Displaced Starburst Amacrine Cells in a Rat Glaucoma Model" (2017). Peer Reviewed Articles. 29.