The Impact of Aging on the Function of Retinal Ganglion Cells

Abstract

Aging is a major risk factor for retinal neurodegenerative diseases. Aged mammalian retinal ganglion cells (RGCs) lack the ability to regenerate axons after injury. Rodent models suggest that older age increases the vulnerability of RGCs to injury and impairs RGC function as well as their functional recovery. Molecular changes – including decreased circulating levels of brain-derived neurotrophic factor (BDNF) – might contribute to impaired RGC dendritic extension during aging. Moreover, age-related mitochondrial dysfunction plays a major role in aging processes, as it leads to reduced adenosine triphosphate and increased generation of reactive oxygen species. Autophagy activity is necessary for the maintenance of cellular homeostasis and decreases with aging in the central nervous system. During aging, vascular insufficiency may lead to impaired oxygen and nutrient supply to RGCs. Microglial cells undergo morphological changes and functional impairment with aging, which might compromise retinal homeostasis and promote an inflammatory environment. Addressing these age-related changes by means of a low-energy diet, exercise, and neurotrophic factors might prevent age-related functional impairment of RGCs. This review focuses on the current understanding of aging RGCs and key players modulating those underlying mechanisms.

Zusammenfassung

Altern ist ein wichtiger Risikofaktor für neurodegenerative Erkrankungen der Netzhaut. Retinale Ganglienzellen (RGZ) können Axone nach Verletzungen nicht regenerieren. Tiermodelle deuten darauf hin, dass zunehmendes Alter die Vulnerabilität der RGZ erhöht und die Funktion der RGZ sowie ihre funktionelle Erholung beeinträchtigt. Molekulare Veränderungen, bspw. verringerte BDNF-Level (Brain-Derived Neurotrophic Factor), können dazu beitragen, dass die dendritische Ausdehnung der RGZ im Alter beeinträchtigt ist. Auch eine altersbedingte mitochondriale Dysfunktion spielt eine wichtige Rolle bei Alterungsprozessen, da sie zu einer Verringerung an Adenosintriphosphat und einer erhöhten Bildung reaktiver Sauerstoffspezies führt. Die Autophagieaktivität ist für die Aufrechterhaltung der zellulären Homöostase notwendig und nimmt mit zunehmendem Alter im zentralen Nervensystem ab. Während des Alterungsprozesses kann außerdem eine vaskuläre Insuffizienz zu einer beeinträchtigten Sauerstoff- und Nährstoffversorgung der RGZ führen. Mikrogliazellen erfahren mit zunehmendem Alter morphologische Veränderungen und funktionelle Beeinträchtigungen, was die retinale Homöostase beeinträchtigen und ein entzündliches Umfeld fördern könnte. Die Behandlung dieser altersbedingten Veränderungen durch kalorienarme Ernährung, Bewegung und neurotrophe Faktoren könnte altersbedingte funktionale Beeinträchtigungen der RGZ verhindern. Diese Übersichtsarbeit konzentriert sich auf den derzeitigen Kenntnisstand hinsichtlich der Funktion alternder RGZ und die Hauptakteure, die die zugrunde liegenden Mechanismen modulieren.

Keywords

retinal ganglion cells - aging - retina - optic nerve - glaucoma

Schlüsselwörter

retinale Ganglienzellen - Altern - Retina - Sehnerv - Glaukom

Publication History

Received: 31 October 2023

Accepted: 19 December 2023

Article published online:
27 February 2024

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