Purpose
Anti-glaucoma surgeries are incresingly useful in decreasing IOP, but they don’t always succeed due to scar formation in the surgery area. We planed to develop a novel PLGA-CsA (Cyclosporine A) drug delivery system based on glaucoma drainage device (GDD) to continuously release anti-scar medication and tested these GDDs using an experimental rabbit model of GDD implantation surgery.
Methods
A glaucoma drainage device similar to Ahmed GDD was prepared by molding a liquid medical silicon, and then a PLGA-CsA (Cyclosporine A) drug delivery layer was coated on it. We tested the function by using scanning electron microscope (SEM) and atomic force microscope (AFM). We observed how the rabbit Tenon’s fibroblasts (RTFs) were influenced in different concentration of CsA to figure out the optimal dose. And we drew the drug-release curve of our GDDs and their effect in inhibiting RTFs in-vitro. Then we implanted 4 groups of GDDs into New Zealand rabbits’ eyes (6 eyes in each group), and focused on the morphology of blebs, the IOP and anterior chamber reaction during the follow up. And we underwent anterior chamber radiography to make sure whether the filtrating pathway was blocked. At last we tried to dig out how our GDDs worked in slowing or preventing the scar formation by means of pathology and immunohistochemistry.
Results
The GDD we developed was able to release CsA in a stable rate; on the other hand, CsA inhibited the growth of Rabbit Tenon’s Fibroblasts (RTFs) in a concentration-dependent and time-dependent way. The drug-release curve showed that our novel GDDs could maintain the CsA in a stable concentration for relatively long time (Figure 1), which was also proved by the direct inhibition study of GDD in-vitro. And compared to ND-NG group the implantation of other three groups of GDDs proved effective in keeping a filtrating pathway for longer time according to the morphology of blebs, the IOP (Figure 2) and anterior chamber radiography and the D-G group was the most effective. The pathology and IHC study showed that our GDDs could decrease scar tissue and increase lymphatic vessels around the surgery area, which might be the key reason why they worked.
Conclusions
The novel PLGA-CsA drug delivery system based on GDDs can effectively prevent postoperative scar formation and improve prognosis in glaucoma therapy.