Neuroprotection

Abstract

The mammalian retina comprises a rich, heterogeneous mosaic of neuronal morphological phenotypes intermeshed in an intricate pattern of synaptic connectivity. This cellular diversity is further amplified by a wide variety of neurochemical phenotypes, defined by specific expression patterns of numerous neurotransmitters, receptors, and transporters, as well as intracellular regulators such as calcium binding proteins. This complexity confers, in part, regional specializations in the retinal wiring and reflects distinct regional metabolic requirements of retinal neurons. An implication of this cellular diversity is that populations of retinal neurons exhibit differential vulnerability to a variety of diseases or injuries, including genetic, environmental, and metabolic insults. The endpoint for all of these insults is neuronal cell death (either necrotic or apoptotic), and a major challenge in ophthalmology is to prevent or delay retinal neuron loss, even in the face of a continued disease process—hence, neuroprotection. Differential, or selective, vulnerability of retinal neurons also suggests multiple potential targets for cell- or pharmacological-based neuroprotective interventions. The goal of this chapter is to review the expression patterns of a number of cellular and molecular targets (i.e., cell surface receptors, intracellular regulators of cell death, and differential sensitivity to trophic factors) that may underlie a particular nerve cell’s predilection for survival or death in the face of disease.