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Inicio Medicina Clínica (English Edition) New frontiers and clinical implications in the pathophysiology of age-related ma...
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Vol. 154. Issue 12.
Pages 496-504 (June 2020)
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Vol. 154. Issue 12.
Pages 496-504 (June 2020)
Review
New frontiers and clinical implications in the pathophysiology of age-related macular degeneration
Nuevas fronteras e implicaciones clínicas en la fisiopatología de la degeneración macular asociada a la edad
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Liria Yamamoto-Rodrígueza, Marco A. Zarbinb, Ricardo P. Casaroli-Maranoa,c,
Corresponding author
rcasaroli@ub.edu

Corresponding author.
a Department of Surgery, School of Medicine (FMCS) & Hospital Clinic de Barcelona, University of Barcelona, Barcelona, Spain
b Institute of Ophthalmology and Visual Science, Rutgers-New Jersey Medical School, Rutgers University, Newark, NJ, USA
c Institute of Biomedical Research – IIB-Sant Pau (SGR1113) & Banc de Sang i Teixits (BST), Barcelona, Spain
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Table 1. Degenerative pathologies related to protein-aggregates.
Abstract

Age-related macular degeneration (AMD) involves progressive degeneration of the central retina, termed the macula, which provides high-acuity vision needed to recognize faces, drive, etc. AMD is the leading cause of blindness in the aging population. A plethora of paradigm-shifting perspectives regarding AMD's multifaceted pathophysiology is emerging. This review will endeavor to gather novel insights and attempts to identify translational implications and new areas of research. The concept of aberrant inflammation being at the center of age-related diseases, particularly AMD, is being received with increasing credence. Retinal angiogenesis, at the forefront of the neovascular complications of AMD (nAMD), is now being understood as an imbalance between trophic factors released by retinal cells secretome. Additionally, mechanisms involving oxidative stress and inflammatory complement pathways have also been identified, along with genetic and other risk factors that play a key role in AMD's onset and progression. Associations have been drawn with AMD and other degenerative deposit diseases such as Alzheimer's disease, atherosclerosis, and glomerulonephritis, which are providing further insight into this maculopathy.

Keywords:
Inflammation
Oxidative stress
Drusen
Inflammasomes
Complement pathway
VEGF
Abbreviations:
AMD
nAMD
AMD
RPE
BM
VEGF
Resumen

La degeneración macular asociada a la edad (DMAE) está caracteriza por un proceso degenerativo progresivo de la retina central —denominada mácula— que es la responsable por la visión de definición. La DMAE es la principal causa de ceguera en la población de la 3.ª edad. Se postulan varias perspectivas de cambio de paradigma con respecto a la fisiopatología multifactorial de esta enfermedad. La presente revisión se centrará en recopilar nuevas ideas e intentos de identificar implicaciones traslacionales, además de nuevas áreas de investigación de la enfermedad. El concepto de inflamación aberrante, que aparece en el centro de las enfermedades asociadas a la edad, y en particular la DMAE, se presenta con creciente credibilidad. La angiogénesis retiniana que se encuentra en la vanguardia de las complicaciones neovasculares de la DMAE se entiende actualmente como un desequilibrio entre los factores tróficos liberados por el secretoma de las células de la retina. Además, también se han identificado mecanismos relacionados con el estrés oxidativo y las vías inflamatorias del complemento que, junto con factores genéticos y otros factores de riesgo, juegan un papel clave en la aparición y en la progresión de la enfermedad. Se han establecido asociaciones entre la DMAE y otras enfermedades degenerativas de depósitos, tales como la enfermedad de Alzheimer, la aterosclerosis y la glomerulonefritis, lo que proporciona información adicional sobre esta maculopatía.

Palabras clave:
Inflamación
Estrés oxidativo
Drusas
Inflamasomas
Vía del complemento
V

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