Diabetic retinopathy (DR) is a multifactorial manifestation associated with microvascular complications and is the fourth leading cause of visual impairment and blindness world-wide. Current day treatment of DR relies heavily on invasive techniques such as intravitreal injections of therapeutic agents. Unfortunately, intravitreal injections are associated with various complications such as intraocular bleeding, endophthalmitis, pain and discomfort resulting in poor patient compliance. To date, there has been no non-invasive drug delivery system reported for DR treatment. To address this, we developed a core-shell nanoparticle-based delivery system consisting of a hydrophobic polycaprolactone core and a hydrophilic Pluronic® F68 shell, loaded with triamcinolone acetonide and evaluated its efficacy in a DR rat model. After being administered as eye drops, the drug loaded nanoparticles significantly improved structural (retinal thickness and vascular health) and functional activity (rod and cone function) of retina as compared to DR controls that were treated with the drug alone or placebo nanoparticles. Furthermore, drug loaded nanoparticles reduced retinal inflammation as evidenced by a decrease in NF-κB, ICAM-1 and TNFα expression after 20 days of treatment. Similarly, a reduction in glial cell hyperplasia as evidenced by reduced GFAP expression, and a decrease in microvascular complications as evidenced by a decrease in VEGF secretion and microvascular tuft formation were observed in rat retinas after 40 days of treatment. The combined reduction in retinal inflammation and vascular abnormalities, both hallmarks of DR, demonstrates the potential of the nanoparticulate delivery system for use as a topical formulation for treating DR.

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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.