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Purpose: Retinal laser photocoagulation is used to treat a variety of retinal diseases. Breakdown of the blood-aqueous barrier has been noted after retinal laser photocoagulation. The effect of vascular endothelial growth factor (VEGF) on the function of the blood-aqueous barrier after retinal laser photocoagulation remains undetermined. The current study was designed to evaluate the relationship between intraocular levels of VEGF and breakdown of the blood-aqueous barrier after retinal laser photocoagulation in rabbits., Methods: Pigmented rabbits were treated with retinal laser photocoagulation in one eye; the other served as control. Laser flare photometry was carried out on post-treatment days 1, 3, 7, and 14. Animals were sacrificed at the time period just mentioned postlaser, the eyes were removed, and samples of vitreous and aqueous humor were collected. Intraocular VEGF levels were measured by using an immunoassay. An intravitreal injection of VEGF was administered, and the aqueous flare intensity and VEGF levels in the aqueous and vitreous humor were measured at the time periods just mentioned., Results: A significant increase in the aqueous flare intensity after retinal laser photocoagulation was noticed on postoperative day 1, with the values returning to baseline levels on day 14. The VEGF levels in the vitreous of the lasered eyes were significantly increased on day 1 compared with the nonlasered control eyes. The VEGF levels in the aqueous humor of the lasered eyes were also significantly increased on day 1 compared with the control eyes. An intravitreal injection of VEGF induced a significant increase in the aqueous flare intensity and VEGF levels in the aqueous and vitreous humor., Conclusions: The current results suggested that retinal laser photocoagulation can produce a breakdown of the blood-aqueous barrier. VEGF may play a role in the blood-aqueous barrier dysfunction after retinal laser photocoagulation.

Importance of the Field: Delivery of drugs to the retina remains a major challenge which needs to be addressed urgently because retinal disorders are leading causes of visual impairment and significantly affect a patient's quality of life. Systemic drug administration is one possible route for treating retinal disorders; however, retinal transfer of drugs from the circulating blood is strictly regulated by two blood-ocular barrier systems, the blood-aqueous barrier and the blood-retinal barrier., Areas Covered in This Review: This review summarizes the latest biological research regarding blood-ocular barrier drug transporters., What the Reader Will Gain: The blood-ocular barrier sites and their respective roles in aqueous humor dynamics and retinal homeostasis are briefly presented. The potential impact of ATP-binding cassette (ABC) and solute carrier (SLC) drug transporters, such as ABCB, ABCC, ABCG, SLC7, SLC16, SLC19, SLCO/SLC21A, SLC22A and SLC29 transporters, on the permeability of drugs across the blood-ocular barriers is then illustrated., Take Home Message: As more information becomes available regarding the blood-ocular barrier transporters, we may be able to design simpler and more effective routes for drug delivery to the retina and, consequently, improve the treatment of retinal diseases.

Research into treatment modalities affecting vision is rapidly progressing due to the high incidence of diseases such as diabetic macular edema, proliferative vitreoretinopathy, wet and dry age-related macular degeneration and cytomegalovirus retinitis. The unique anatomy and physiology of eye offers many challenges to developing effective retinal drug delivery systems. Historically, drugs have been administered to the eye as liquid drops instilled in the cul-de-sac. However retinal drug delivery is a challenging area. The transport of molecules between the vitreous/retina and systemic circulation is restricted by the blood-retinal barrier, which is made up of retinal pigment epithelium and endothelial cells of the retinal blood vessels. An increase in the understanding of drug absorption mechanisms into the retina from local and systemic administration has led to the development of various drug delivery systems, such as biodegradable and non-biodegradable implants, microspheres, nanoparticles and liposomes, gels and transporter-targeted prodrugs. Such diversity in approaches is an indication that there is still a need for an optimized noninvasive or minimally invasive drug delivery system to the eye. A number of large molecular weight compounds (i.e., oligonucleotides, RNA aptamers, peptides and monoclonal antibodies) have been and continue to be introduced as new therapeutic entities. However, for high molecular weight polar compounds the mechanism of epithelial transport is primarily through the tight junctions in the retinal pigment epithelium, as these agents undergo limited transcellular diffusion. Delivery and administration of these new drugs in a safe and effective manner is still a major challenge facing pharmaceutical scientists. In this review article, the authors discuss various drug delivery strategies, devices and challenges associated with drug delivery to the retina.