Subchapter 1.4 - Receptors, ion channels, and signal transduction pathways as targets for drug intervention to mitigate ocular diseases

Abstract

Coordinated communication between and within cells forms the basis for life in health and disease of all tissues and organs. Such relaying of information is mediated by neurotransmitters, hormones, bacteria, viruses, steroids, and a host of cyto- and chemokines via specific receptors, ion channels, and transporters located in cellular membranes and intracellular organelles including the nuclear membrane and within the nucleus itself. Activation of such transmembrane components generates intracellular second messengers such as cyclic adenosine monophosphate, cyclic guanine monophosphate, inositol phosphates, diacylglycerol, Ca2+, and gaseous transmitters such as nitric oxide and hydrogen sulfide that modulate the activity of cytoplasmic proteins, lipids, and other substances via phosphorylation, dephosphorylation, glycation, and acetylation. Additional communication is achieved by modulation of genetic machinery, via transcription factors, various chaperones, and through secretome/exosome-mediated release of growth factors, microRNAs, and via direct transfer of many of the afore-mentioned chemicals between neighboring cells down nanotunnels. Dysfunctions within any component of this signal transduction machinery, whether in excess or deficiency or by mutation, result in some form of diseases and thus represent targets for intervention by small molecule drugs, peptides, antibodies, genetic manipulation, and/or via cell-replacement therapeutics. A brief outline of some of these elements will be discussed.