Age-related macular degeneration (AMD) is a leading cause of visual impairment worldwide, characterized by the accumulation of extracellular drusen deposits within the macula. The pathogenesis of AMD is multifactorial, involving oxidative stress, chronic inflammation, immune system dysregulation, and genetic predisposition. A key contributor to disease progression is the excessive accumulation of reactive oxygen species (ROS), which damage retinal pigment epithelium (RPE) cells and disrupt cellular homeostasis. Additionally, immunosenescence and chronic low-grade inflammation exacerbate AMD pathology, further impairing retinal integrity. Despite ongoing research, effective therapeutic options remain limited, and there is no definitive cure for AMD. This review explores the intricate molecular mechanisms underlying AMD, including the role of oxidative stress, chronic inflammation, and genetic factors in RPE dysfunction. Furthermore, we highlight potential therapeutic strategies targeting these pathways, as well as the emerging role of bioinformatics and artificial intelligence in AMD diagnosis and treatment development. By improving our understanding of AMD pathophysiology, we can advance the search for novel therapeutic interventions and preventative strategies.

In patients with age-related macular degeneration (AMD), the crucial retinal pigment epithelial (RPE) cells are characterized by mitochondria that are structurally and functionally defective. Moreover, deficient expression of the mRNA-editing enzyme Dicer is noted specifically in these cells. This Dicer deficit up-regulates expression of Alu RNA, which in turn damages mitochondria—inducing the loss of membrane potential, boosting oxidant generation, and causing mitochondrial DNA to translocate to the cytoplasmic region. The cytoplasmic mtDNA, in conjunction with induced oxidative stress, triggers a non-canonical pathway of NLRP3 inflammasome activation, leading to the production of interleukin-18 that acts in an autocrine manner to induce apoptotic death of RPE cells, thereby driving progression of dry AMD. It is proposed that measures which jointly up-regulate mitophagy and mitochondrial biogenesis (MB), by replacing damaged mitochondria with “healthy” new ones, may lessen the adverse impact of Alu RNA on RPE cells, enabling the prevention or control of dry AMD. An analysis of the molecular biology underlying mitophagy/MB and inflammasome activation suggests that nutraceuticals or drugs that can activate Sirt1, AMPK, Nrf2, and PPARα may be useful in this regard. These include ferulic acid, melatonin urolithin A and glucosamine (Sirt1), metformin and berberine (AMPK), lipoic acid and broccoli sprout extract (Nrf2), and fibrate drugs and astaxanthin (PPARα). Hence, nutraceutical regimens providing physiologically meaningful doses of several or all of the: ferulic acid, melatonin, glucosamine, berberine, lipoic acid, and astaxanthin, may have potential for control of dry AMD.

Annona muricata L. is a tropical tree that is used in traditional medicine around the world. The high content of flavonoid, alkaloid, acetogenin, phenolic and lipophilic compounds of this tropical tree forms the basis of its traditional medical uses. Our objective was to study soursop leaf extracts to support their use as antiviral therapies and investigate their protective effects against oxidative damage. The aqueous extract (AE) and acidified ethanolic extract (AEE) of soursop leaves were characterized by ultra performance liquid chromatography (UPLC), and their effects on human erythrocytes and in vitro antioxidant capacity, as evaluated by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid (ABTS) assays, were investigated. The antiviral effects were evaluated using a bacteriophage surrogate. AEE showed the highest phenolic content, with rutin as the predominant compound. This extract showed higher values in the DPPH and ABTS assays, with 23.61 ± 0.42 and 24.91 ± 0.16 mmol of Trolox equivalent per gram, respectively. Inhibition of hemolysis was 34% and 51% for AE and AEE, respectively. AEE was selected for the antiviral study because of its higher antioxidant activity. The viral reduction ranged from 5–6 log10 plaque-forming units/volume (PFU) at contact times of 15–360 min. Soursop leaves have a positive effect on reducing oxidative stress in human erythrocytes and viral infections.