Aging Effects on Optic Nerve Neurodegeneration

Abstract

Common risk factors for many ocular pathologies involve non-pathologic, age-related damage to the optic nerve. Understanding the mechanisms of age-related changes can facilitate targeted treatments for ocular pathologies that arise at any point in life. In this review, we examine these age-related, neurodegenerative changes in the optic nerve, contextualize these changes from the anatomic to the molecular level, and appreciate their relationship with ocular pathophysiology. From simple structural and mechanical changes at the optic nerve head (ONH), to epigenetic and biochemical alterations of tissue and the environment, multiple age-dependent mechanisms drive extracellular matrix (ECM) remodeling, retinal ganglion cell (RGC) loss, and lowered regenerative ability of respective axons. In conjunction, aging decreases the ability of myelin to preserve maximal conductivity, even with “successfully” regenerated axons. Glial cells, however, regeneratively overcompensate and result in a microenvironment that promotes RGC axonal death. Better elucidating optic nerve neurodegeneration remains of interest, specifically investigating human ECM, RGCs, axons, oligodendrocytes, and astrocytes; clarifying the exact processes of aged ocular connective tissue alterations and their ultrastructural impacts; and developing novel technologies and pharmacotherapies that target known genetic, biochemical, matrisome, and neuroinflammatory markers. Management models should account for age-related changes when addressing glaucoma, diabetic retinopathy, and other blinding diseases.

The Role of Oxidative Stress in the Aging Eye

“…Age-related changes of the optic nerve include swelling of axons at the lamina cribrosa, a reduction in nerve fiber density, and an increase in connective tissue composition such as elastic fibers [ 4 , 93 , 94 , 95 , 96 ]. Furthermore, neural rim volume and minimum rim width of the optic nerve head appear to decline with advancing age [ 97 ].…”

Extracellular‐Matrix Mechanics Regulate the Ocular Physiological and Pathological Activities

“…ECM is constantly remodeled in the optic nerve, and its various components, including glycoproteins fbronectin, laminin, tenascin-C, and tenascin-R as well as the chondroitin sulfate proteoglycans (CSPGs), aggrecan, neurocan, and brevican, are critical for maintaining the normal function of the optic nerve [68][69][70]. Tenascin-R can modulate neurite outgrowth as well as neural and glial adhesion, whereas tenascin-C is increased and engaged in neuroinfammation and glial response under pathological conditions, and CSPG is highly aggregated in glial scars, limiting axon's ability to regenerate [44,71].…”

Normal diameter of the optic nerve using magnetic resonance imaging: A retrospective Nigerian study

“…[ 2 ] Myelination of the ON occurs at 8 weeks of gestation following the proliferation of oligodendrocytes. [ 3 ] The ON is 25 mm long with a small cross-sectional area (2.8–4.27 mm 2 ) at birth. It grows exponentially (80%) in the first 3–4 years of age.…”

“…Thereafter, it shows a slow increase in growth within the first two decades and reaches the adult length (40–45 mm) and width (3.4 mm) by 12–15 years, after which, it remains constant. [ 1 3 ]…”

“…The ON has two types of fibers; the deep smaller fibers (macular fibers) which carry information responsible for central vision and the larger peripheral fibers which carry information originating from the peripheral retinal cells. [ 3 ] Beyond the lamina cribrosa, the nerve is myelinated and fully encapsulated by meningeal sheath and cerebrospinal fluid. [ 4 ] The ON has four parts.…”