Thomas B. Connor

Retinal diseases are one of the leading causes of blindness globally. The mainstay treatments for these blinding diseases are laser photocoagulation, vitrectomy, and repeated intravitreal injections of anti-vascular endothelial growth factor (VEGF) or steroids. Unfortunately, these therapies are associated with ocular complications like inflammation, elevated intraocular pressure, retinal detachment, endophthalmitis, and vitreous hemorrhage. Recent advances in nanomedicine seek to curtail these limitations, overcoming ocular barriers by developing non-invasive or minimally invasive delivery modalities. These modalities include delivering therapeutics to specific cellular targets in the retina, providing sustained delivery of drugs to avoid repeated intravitreal injections, and acting as a scaffold for neural tissue regeneration. These next-generation nanomedicine approaches could potentially revolutionize the treatment landscape of retinal diseases. This review describes the availability and limitations of current treatment strategies and highlights insights into the advancement of future approaches using next-generation nanomedicines to manage retinal diseases.

Damage-associated molecular patterns (DAMPs) are endogenous danger molecules released from the extracellular and intracellular space of damaged tissue or dead cells. Recent evidence indicates that DAMPs are associated with the sterile inflammation caused by aging, increased ocular pressure, high glucose, oxidative stress, ischemia, mechanical trauma, stress, or environmental conditions, in retinal diseases. DAMPs activate the innate immune system, suggesting their role to be protective, but may promote pathological inflammation and angiogenesis in response to the chronic insult or injury. DAMPs are recognized by specialized innate immune receptors, such as receptors for advanced glycation end products (RAGE), toll-like receptors (TLRs) and the NOD-like receptor family (NLRs), and purine receptor 7 (P2X7), in systemic diseases. However, studies describing the role of DAMPs in retinal disorders are meager. Here, we extensively reviewed the role of DAMPs in retinal disorders, including endophthalmitis, uveitis, glaucoma, ocular cancer, ischemic retinopathies, diabetic retinopathy, age-related macular degeneration, rhegmatogenous retinal detachment, proliferative vitreoretinopathy, and inherited retinal disorders. Finally, we discussed DAMPs as biomarkers, therapeutic targets, and therapeutic agents for retinal disorders.

Retinal diseases such as age-related macular degeneration (AMD), retinopathy of prematurity (ROP), and diabetic retinopathy (DR) are the leading causes of visual impairment worldwide. There is a critical need to understand the structural and cellular components that play a vital role in the pathophysiology of retinal diseases. One potential component is the family of structural proteins called small leucine-rich proteoglycans (SLRPs). SLRPs are crucial in many fundamental biological processes involved in the maintenance of retinal homeostasis. They are present within the extracellular matrix (ECM) of connective and vascular tissues and contribute to tissue organization and modulation of cell growth. They play a vital role in cell–matrix interactions in many upstream signaling pathways involved in fibrillogenesis and angiogenesis. In this comprehensive review, we describe the expression patterns and function of SLRPs in the retina, including Biglycan and Decorin from class I; Fibromodulin, Lumican, and a Proline/arginine-rich end leucine-rich repeat protein (PRELP) from class II; Opticin and Osteoglycin/Mimecan from class III; and Chondroadherin (CHAD), Tsukushi and Nyctalopin from class IV.