**Background:** Retinal degenerative diseases, including age-related macular degeneration (AMD), glaucoma, retinitis pigmentosa (RP), and diabetic retinopathy (DR), are leading causes of visual impairment and blindness worldwide. These conditions involve progressive loss of photoreceptors, retinal ganglion cells (RGCs), or supporting cells, driven by genetic, metabolic, and environmental factors. Understanding the molecular and biochemical hallmarks is critical for developing effective therapies.
**Methods:** This is a narrative review that searched the PubMed database for publications from the past five years, supplemented by older reputable references, focusing on diseases affecting posterior eye structures: AMD, glaucoma, RP, and DR. The review synthesizes information on pathophysiology, molecular markers, genetic factors, and therapeutic approaches.
**Key Results:**
- **AMD:** Affects approximately 9% of blindness cases; projected to affect 288 million people by 2040. Key hallmarks include drusen (yellow-white deposits), geographic atrophy, and macular neovascularization. Genetic risk factors include mutations in *cfh* and *arms2–htra1*. Oxidative stress and Bruch's membrane changes are central. Therapies include anti-VEGF agents (e.g., bevacizumab, ranibizumab, faricimab), complement inhibitors (pegcetacoplan, avacincaptad pegol), and DARPin-based therapies.
- **Glaucoma:** Affects over 80 million people globally (2020), projected to reach 111 million by 2040. Primary open-angle glaucoma (POAG) is the most common form. Hallmarks include elevated intraocular pressure (IOP), optic nerve damage, and visual field loss. Genetic studies identified 127 associated genes, including *myoc*, *optn*, *wdr36*, *cyp1b1*, and *thbs1*. Therapies target IOP reduction (prostaglandin analogs, beta-blockers, carbonic anhydrase inhibitors, Rho-kinase inhibitors) and emerging neuroprotective strategies (e.g., CaMKII activation, sigma 1 receptor agonists, gene therapy with AAV vectors).
- **Retinitis Pigmentosa (RP):** Prevalence 1 in 5000; most common inherited retinal dystrophy. Over 80 genes implicated, with *rho*, *ush2a*, and *rpgr* accounting for ~30% of cases. Pathological mechanisms include protein misfolding, ER stress, apoptosis, and ciliary transport dysfunction. Gene therapy (Luxturna® for *rpe65* mutations) is approved. Other approaches include chemical chaperones, neurotrophic factors, and antioxidants.
- **Diabetic Retinopathy (DR):** Affects ~93 million people worldwide; one in three diabetics will develop DR. Risk factors include prolonged diabetes, poor glycemic control (1% HbA1c reduction reduces risk by 40%), hypertension (10 mmHg decrease reduces vision loss risk by 50%). Molecular pathways include polyol pathway activation, AGE formation, PKC activation, oxidative stress, and inflammation. Genetic associations include *vegf*, *ace*, *aldr2*, and *enos*. Therapies include anti-VEGF intravitreal injections (ranibizumab, bevacizumab, aflibercept), laser photocoagulation (17% risk reduction in DME), and corticosteroids (dexamethasone, fluocinolone acetonide).
**Clinical Implications:** The review underscores the importance of early diagnosis through advanced imaging and genetic testing. Current treatments primarily manage symptoms or slow progression, but gene therapies and targeted molecular interventions offer hope for halting or reversing degeneration. Continued research into biomarkers and novel pharmacological targets is essential to reduce the global burden of retinal diseases.