The retina and, in particular, retinal pigment epithelial cells are unusual for being encumbered by exposure to visible light, while being oxygen-rich, and also amassing photoreactive molecules. These fluorophores (bisretinoids) are generated as a byproduct of the activity of vitamin A aldehyde—the chromophore necessary for vision. Bisretinoids form in photoreceptor cells due to random reactions of two molecules of vitamin A aldehyde with phosphatidylethanolamine; bisretinoids are subsequently transferred to retinal pigment epithelial (RPE) cells, where they accumulate in the lysosomal compartment with age. Bisretinoids can generate reactive oxygen species by both energy and electron transfer, and they become photo-oxidized and photolyzed in the process. While these fluorescent molecules are accrued by RPE cells of all healthy eyes, they are also implicated in retinal disease.

Age-related macular degeneration (AMD) severely affects central vision due to progressive macular degeneration and its staggering prevalence is rising globally, especially in the elderly population above 55 years. Increased oxidative stress with aging is considered an important contributor to AMD pathogenesis despite multifaceted risk factors including genetic predisposition and environmental agents. Wet AMD can be managed with routine intra-vitreal injection of angiogenesis inhibitors, but no satisfactory medicine has been approved for the successful management of the dry form. The toxic carbonyls due to photo-oxidative degradation of accumulated bisretinoids within lysosomes initiate a series of events including protein adduct formation, impaired autophagy flux, complement activation, and chronic inflammation, which is implicated in dry AMD. Therapy based on antioxidants has been extensively studied for its promising effect in reducing the impact of oxidative stress. This paper reviews the dry AMD pathogenesis, delineates the effectiveness of dietary and nutrition supplements in clinical studies, and explores pre-clinical studies of antioxidant molecules, extracts, and formulations with their mechanistic insights.

Mass spectrometry-based molecular imaging has been utilized to map the spatial distribution of target metabolites in various matrixes. Among the diverse mass spectrometry techniques, matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS) is the most popular for molecular imaging due to its powerful spatial resolution. This unparalleled high resolution, however, can paradoxically act as a bottleneck when the bio-imaging of large areas, such as a whole plant, is required. To address this issue and provide a more versatile tool for large scale bio-imaging, direct analysis in real-time-time of flight-mass spectrometry (DART-TOF-MS), an ambient ionization MS, was applied to whole plant bio-imaging of a medicinal plant, Ephedrae Herba. The whole aerial part of the plant was cut into 10–20 cm long pieces, and each part was further cut longitudinally to compare the contents of major ephedra alkaloids between the outer surface and inner part of the stem. Using optimized DART-TOF-MS conditions, molecular imaging of major ephedra alkaloids of the whole aerial part of a single plant was successfully achieved. The concentration of alkaloids analyzed in this study was found to be higher on the inner section than the outer surface of stems. Moreover, side branches, which are used in traditional medicine, represented a far higher concentration of alkaloids than the main stem. In terms of the spatial metabolic distribution, the contents of alkaloids gradually decreased towards the end of branch tips. In this study, a fast and simple macro-scale MS imaging of the whole plant was successfully developed using DART-TOF-MS. This application on the localization of secondary metabolites in whole plants can provide an area of new research using ambient ionization mass spectroscopy and an unprecedented macro-scale view of the biosynthesis and distribution of active components in medicinal plants.

Significance: Taurine is a sulfur-containing amino acid that is not incorporated into protein but is abundant in retina. Schiff base adducts that form nonenzymatically and reversibly from reactions between taurine and vitamin A aldehyde (A1T) are increased under conditions in which the visual chromophore 11- cis -retinal is more abundant. These settings include black versus albino mice, dark-adapted versus light-adapted mice, and mice expressing the Rpe65-Leu450 versus Rpe65-Met450 variant. Conversely, A1T is less abundant in mouse models deficient in 11- cis -retinal. As an amphiphile, protonated A1T may serve to facilitate retinoid trafficking and could constitute a small-molecule reserve of mobilizable 11- cis -retinal in photoreceptor cells.

Dry age-related macular degeneration (AMD) is the leading cause of central vision loss among the elderly, yet no curative treatment exists. While exudative AMD can be managed with anti-vascular endothelial growth factor (VEGF) therapy, dry AMD—accounting for more than 85% of cases—progresses insidiously from drusen accumulation to geographic atrophy (GA). Although the recent U.S. Food and Drug Administration (FDA) approvals of pegcetacoplan and avacincaptad pegol represent major milestones, their therapeutic effects remain modest. This review provides an integrated overview of the molecular and cellular mechanisms underlying dry AMD, highlighting key pathogenic pathways involving oxidative stress, lipid dysregulation, complement activation, mitochondrial impairment, and RPE-specific bisretinoid lipofuscin accumulation. We further summarize mechanistic mouse models that replicate these pathological processes and discuss how each model contributes to understanding the disease. Finally, we review current and emerging therapeutic strategies—including complement inhibitors, visual cycle modulators, and mitochondrial-protective approaches—and outline future directions for translational research. Collectively, this review synthesizes mechanistic insights, disease models, and therapeutic innovation to support the development of targeted and stage-specific interventions for dry AMD.