Pathological Eye Growth in Myopia: a Limited Review on Endocrine Physiology for Future Research

Abstract

Purpose: Myopia or short-sightedness: first manifests in school-children (early-onset), and also in young adults (late-onset). Pathological myopia can lead to stretching of the eyeball to the point of blindness from a detached retina. This title presents a preliminary understanding of endocrine, juxtacrine, and paracrine factors: hoping to stimulate further research and enable early therapeutic intervention. Background: The optical stimulus for eye growth is a blurred image on the retina that results from under-focused accommodation of the internal crystalline lens. Neural signals and biochemical messaging from the retina and vascular choroid provide local impetus to alter collagen structure in the outer white sclera of the eye. In persons that develop highly myopic refractive error, additional factors from blood and tissue chemistry, might influence intra-ocular pressure (IOP), posited to influence eyeball elongation. New research shows that GABA and dopamine are involved, but other factors remain unexplored. Eye Physiology: Human sclera has developmental origination same as any other connective tissue derived from the neural crest and mesoderm. Bundles of collagen fibers exist in the white opaque sclera and are more stringently oriented in the dome of the clear, transparent cornea. “Deformation compliance” of the sclera is governed by complexity of the collagen architecture, and “reduced scleral rigidity” is a known factor for myopic elongation, but developmental physiology is not well understood. Muscular contraction is required for sustained eye focusing to objects located at normal working distances. Short-term contractions can reduce IOP but increased muscle density from sustained near accommodation can promote progression of myopia. This implicates nitric oxide and calcium channels, and a role for associated biochemical and nutritional agonists and antagonists. Endocrine Influences: In his 1954 lecture to the Royal College of Surgeons, Dr. Howard C. Naffziger pointed to all forms of “ocular protrusion,” not just “thyroid exophthalmos,” as being physiologically related. A 2016 review paper on autonomic nervous physiology, aside from sympathetic (adrenergic) and parasympathic (collinergic) control, also implicates Substance P (SP), Vasoactive Intestinal Peptide (VIP), and Phospholipase C (PC). These topics are further described in limited detail. SP is a neuropeptide of the tachykinin family, is released from the terminals of sensory nerves, and regulates emotion (hypothalamus, amygdala, and the periaqueductal gray). It is also a vasodilator dependent on release of nitric oxide. Experimental eye physiology and clinical research pertaining to these topics appears warranted. VIP regulates cardiac contractions, relaxes smooth muscle of the trachea, and affects prolactin secretion by the pituitary gland. Cardiac contractions lead to pulsations of eye pressure about three times in two seconds, and pulmonary effects on IOP occur once every five seconds. Research into these mechanisms requires cross-disciplinary collaborations. PC is a membrane-associated enzyme that cleaves dietary phospholipids and has downstream effects on calcium channels. Binding to blood platelets, of agonists such as thrombin, epinephrine, or collagen: activates PC to release arachidonic acid from cleavage of phosphatidylinositol and phosphatidyl choline. Behavioral effects include visual attention-span and memory: both of which also concern education of children, and effectiveness of adults at work. Conclusions: The author is pleased to report growing interest and evidence for endocrine influences upon the outer coat of the eye (cornea and sclera). A 2022 study on “keratoconus” from Texas and Oklahoma provides in-vitro as well as in-vivo data, suggesting the existence of what they call, the Hypothalamic-Pituitary-Adrenal-Corneal axis. Effective communication across university disciplines and clinic doctors appears necessary for further progress. Funding: The author received no funds from Federal or State granting mechanisms, and no wages from corporate employers. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.