Retinal microenvironment imbalance in dry age-related macular degeneration: a mini-review

Abstract

Background: Age-related macular degeneration (AMD) is the leading cause of blindness in the western world. To prevent what will certainly be a tremendous health and economic burden, effective therapeutics for AMD are urgently needed. To develop these agents in a timely fashion, the molecular pathways that cause disease progression must be elucidated.

Objective: To briefly describe the clinical features of AMD, and review the current understanding of the molecular basis of AMD.

Methods: A literature review.

Results: The discussion will primarily focus on the interplay of oxidative stress and complement dysregulation and the resulting chronic proinflammatory state thought to be central in AMD pathogenesis.

Conclusions: Oxidative stress and complement dysregulation play a substantive role in the development of AMD.

Figure 1

Ocular anatomy relevant to AMD. A. Cross-section of an eye showing the retina and neighboring anatomic structures. B. Histological cross-section of the retina moving inward along the path of incident light include the vitreous (V); Nerve fiber layer (NF) consisting of axons of the third neuron; Ganglion cell layer (G) consisting of the cell nuclei of the multipolar ganglion cells of the third neuron; Inner plexiform layer (IP) consisting of synapses between the axons of the second neuron and dendrites of the third neuron; Inner nuclear layer (IN) containing cell nuclei of the bipolar nerve cells on the second neuron, horizontal cells, and amacrine cells; Photoreceptors (P) consisting of rods and cones; Retinal pigment epithelium (RPE) consisting of a single cubic layer of heavily pigmented epithelial cells; Bruch’s membrane (BM) the matrix separating the RPE from the choroid; Choroid (C), the vasculature between the retina and sclera. C. Fundoscopic image showing the macula located between vascular arcades including the retinal artery (A) and vein (V) with the fovea (*) at the center, approximately 3 mm temporal to the optic nerve (N). Images courtesy of the National Eye Institute.

Figure 2

A. Fundus photo of a right eye with non-neovascular (dry) AMD. Note the numerous large yellow drusen deposits. B. Fundus photo of a left eye with geographic atrophy characteristic of advanced AMD. Note area where RPE cells are absent (arrow). (c) Fundus photo of a right eye with neovascular or wet AMD. Note subretinal hemorrhage (arrow) adjacent to a choroidal neovascular membrane (arrowhead). Wet AMD image, courtesy of the National Eye Institute.

Figure 3

Model of oxidative stress and resulting protective or pathologic immune response. Through the antioxidant systems including the Nrf2 signaling system and the innate immune system’s activation by oxidation specific epitopes (OSEs) the retinal microenvironment can prevent itself from oxidative damage. When overwhelmed by exogenous stressors such as cigarette smoke, chronic inflammation may result leading to a pathologic immune response.