Age-Related Macular Degeneration (AMD): Pathophysiology, Drug Targeting Approaches, and Recent Developments in Nanotherapeutics

Abstract

The most prevalent reason for vision impairment in aging inhabitants is age-related macular degeneration (AMD), a posterior ocular disease with a poor understanding of the anatomic, genetic, and pathophysiological progression of the disease. Recently, new insights exploring the role of atrophic changes in the retinal pigment epithelium, extracellular drusen deposits, lysosomal lipofuscin, and various genes have been investigated in the progression of AMD. Hence, this review explores the incidence and risk factors for AMD, such as oxidative stress, inflammation, the complement system, and the involvement of bioactive lipids and their role in angiogenesis. In addition to intravitreal anti-vascular endothelial growth factor (VEGF) therapy and other therapeutic interventions such as oral kinase inhibitors, photodynamic, gene, and antioxidant therapy, as well as their benefits and drawbacks as AMD treatment options, strategic drug delivery methods, including drug delivery routes with a focus on intravitreal pharmacokinetics, are investigated. Further, the recent advancements in nanoformulations such as polymeric and lipid nanocarriers, liposomes, etc., intended for ocular drug delivery with pros and cons are too summarized. Therefore, the purpose of this review is to give new researchers an understanding of AMD pathophysiology, with an emphasis on angiogenesis, inflammation, the function of bioactive lipids, and therapy options. Additionally, drug delivery options that focus on the development of drug delivery system(s) via several routes of delivery can aid in the advancement of therapeutic choices.

Keywords: age-related macular degeneration; anti-VEGF agents; chronic disease; gene therapy; inflammation; nanomedicine; oxidative stress.

Figure 4

Role of anti-inflammatory therapy on AMD. Modified from [112].

Figure 1

Interplay of aging, genetics, and environmental factors on the pathophysiology of AMD. retinal pigment epithelium (RPE), blood-retinal barrier (BRB), Complement factor H (CFH) gene, and CFH-related gene 1 (CFHR-1).

Figure 2

Role of molecular mediators in Angiogenesis.

Figure 3

Diagram illustrating FGF2’s dual function in the development of fibrotic scars and angiogenesis in the retinal macrophage cell. RBM-007 can inhibit FGF2 and VEGF to prevent scar formation and angiogenesis.

Figure 5

Various plausible ocular drug delivery with their pros and cons.

Figure 6

Diagrammatic representation of various probable nanoformulations that can be applied as an ocular drug delivery system for treatment or diagnostic purposes.