Abstract
Atrophic age-related macular degeneration (AMD) is the most common form of AMD accounting for 90% of patients. During atrophic AMD the waste/exchange pathway between the blood supply (choroid) and the retinal pigment epithelium (RPE) is compromised. This results in atrophy and death of the RPE cells and subsequently the photoreceptors leading to central blindness. Although the mechanisms behind AMD are unknown, the growth of fatty deposits known as drusen, have been shown to play a role in the disease. There is currently no treatment or cure for atrophic AMD. Much research focuses on developing a synthetic substrate in order to transplant healthy cells to the native Bruch’s membrane (BM), however, the diseased native BM and related structures still leave potential for transplanted cells to succumb to disease. In this proof-of-concept work we electrospun poly(ethylene terephthalate) (PET) to fabricate a nanofibrous cytocompatible synthetic BM. The apical surface of the membrane was cultured with ARPE-19 cells and the underside was decorated with poly(lactic acid-co-glycolic acid) (PLGA) or poly(glycolic acid) (PGA) degradable nanoparticles by electrospraying. The membrane exhibited hydrophilicity, high tensile strength and structurally resembled the native BM. ARPE-19 cells were able to form a monolayer on the surface of the membrane and no cell invasion into the membrane was seen. The presence of both PLGA and PGA nanoparticles increased ARPE-19 cell metabolism but had no effect on cell viability. There was a decrease in pH of ARPE-19 cell culture media 7 days following culturing with the PLGA nanoparticles but this change was eliminated by 2 weeks; PGA nanoparticles had no effect on cell culture media pH. The fluorescent dye FITC was encapsulated into nanoparticles and showed sustained release from PLGA nanoparticles for 2 weeks and PGA nanoparticles for 1 day. Future work will focus on encapsulating biologically active moieties to target drusen. This could allow this novel bioactive substrate to be a potential treatment for atrophic AMD that would function two-fold: deliver the required monolayer of healthy RPE cells to the macula on a synthetic BM and remove diseased structures within the retina, restoring the waste/exchange pathway and preventing vision loss.
Highlights
Age-related macular degeneration (AMD) is a progressive disease of the retina that is the leading form of blindness in developed countries
Surface chemistry was analyzed for presence of functional groups following surface treatment and hydrophilic properties measured using water contact angle (WCA)
In this article we have described the development of a proofof-concept composite bioactive membrane that has adequate mechanical properties, permeability and cytocompatibility
Summary
Age-related macular degeneration (AMD) is a progressive disease of the retina that is the leading form of blindness in developed countries. It is a form of central blindness that mainly affects people over the age of 50 years. Neovascular (or wet) AMD makes up 10% of all reported cases where new abnormal leaking blood vessels break through a layer underlying the retina called the BM leading to a loss of central vision. Nonexudative (or dry) AMD, makes up 90% of all cases It is associated with a slowly progressive form of sight loss where fatty deposits known as drusen, form on BM leading to alterations and atrophy of the RPE. Several risk factors for nonexudative AMD are known, there are no available treatments other than supportive optical aids and nutritional supplements that are recommended for a subset of patients with large drusen (Rudolf et al, 2008; Age-Related Eye Disease Study 2 Research Group, 2013)
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