Diabetes Type 4: A Paradigm Shift in the Understanding of Glaucoma, the Brain Specific Diabetes and the Candidature of Insulin as a Therapeutic Agent

In the present analysis, we aim at probing into many important mechanisms that serve to bridge conceptual gaps to fill up the mosaic of a picture revealing that glaucoma indeed is brain specific diabetes and more appropriately “Diabetes Type 4”. Based on this conceptual substance, we weave a novel idea of insulin being a potential remedy for glaucoma. This analysis synthesizes upon the published literature on brain changes in glaucoma, possibility of isolated brain diabetes, insulin signaling glitches in glaucoma pathology, mitochondrial dysfunction and insulin resistance in glaucomatous eyes, insulin mediated regulation of intraocular pressure and its dysregulation in mitochondrial dysfunction. We also look into the role of amyloidopathy and taupathy in glaucoma pathogenesis vis-à-vis insulin signaling. At every step, the discussion reveals that insulin and other allied moieties are a sure promise for glaucoma treatment and management. In this article, we aim at synthesizing a persuasive and all inclusive picture of glaucoma etiopathomechanism centered on “insulin-hypofunctionality” in the central nervous system (i.e. brain specific diabetes). We start with considering the possibility of neurodegenerative diabetes that exists independent of the peripheral diabetes. Once that condition is met, then a metabolic conglomeration of this brain specific diabetes is deliberated upon leading us to understand the development of retinal ganglion cell apoptosis, intraocular pressure elevation, optic cupping and mitochondrial dysfunction. All these are the hallmarks and sufficient conditions to satisfy the diagnostic criteria for glaucoma. Immediate application of this analysis points towards glaucoma therapy centered upon improving what we have termed insulin-hypofunctionality. Keywords: Alzheimer's disease, brain, central nervous system, diabetes, glaucoma, inflammation, insulin, insulin resistance, intraocular pressure, mitochondria, neurodegeneration, neuron, optic nerve, retina.