generating stem cells and introducing the mature cells into the retina. Genetically modified embryonic stem cells have been shown to survive for a prolonged period of time when administered intravitreally into the retinal tissue (Gregory-Evans et al. 2009). Mouse embryonic stem (mES) cells were genetically engineered to overexpress glial cell-derived neurotrophic factor (GDNF). Four microliters of cell suspension­ (50,000 cells/mL) was injected into the vitreous of rat eyes of the test group; control group received either unengineered mES cell suspension or PBS buffer. A statistical increase in the photoreceptor cells were observed in the test group as compared to the control group. Adverse events included retinal detachment, endophthalmitis, and lens opacity. In another study, retinal progenitor cells (RPC) were isolated from human placental alkaline phosphatase (hPAP)-positive embryonic day 17 (E17) rat retina and were transplanted in the subretinal space of transgenic rats via transscleral route (Qiu et al. 2005). The morphology of the cells in the transplant was similar to those in the normal rat eye. The RPC cells were found to be immunoreactive to a variety of antibodies like calbindin, rhodopsin, and protein kinase C, suggesting that the cells were well integrated into the retina of the rat eye. The RPC stem cells were observed 1 month later in the rat eye using an immunohistochemistry assay. There were no retinal hemorrhages or detachments, vitreous opacities, or other signs of intraocular inflammation or clinical toxicity at week two and four after transplantation as seen under ophthalmoscope and confirmed by optical­ coherence tomography (OCT). Stem cell research is currently underway to quantify the gain in visual acuity as well as to assess the stem cell transplant efficiency.

17.4.6  Implants

Implants are regularly used in ophthalmic diseases for providing sustained drug delivery. In 2005, Retisert® (Bausch and Lomb) was approved by the FDA for the treatment of noninfectious uvetis. It is a nonbiodegradable implant comprised of fluocinolone acetonide (active ingredient) in a silicone/polyvinyl alcohol polymer coating situated on a polyvinyl suture that can effectively release fluocinolone ­acetonide for as long as two and half years (Jaffe et al. 2006). The disadvantage of this system is that it must be inserted and removed by a surgeon. The advantage is that patients are not subjected to frequent injections and doctor visits.

NT-501(Neurotech, USA), a polymer capsule implant for intravitreal injection that is currently in clinical trials involves the use of ECT. This implant works by culturing a cell to secrete certain proteins or peptides in a slow release fashion. A phase III trial of ECT is currently underway involving genetically engineered cells capable of secreting CNTF for treating RP and nonneovascular AMD. In the phase I study (Tao et al. 2002; Sieving et al. 2006), capsules of cells transfected with CNTF were surgically implanted in the right eye of ten participants suffering from retinal neurodegeneration. Six months later when the implants were removed, the implant contained viable cells and the CNTF level was found to be still at a ­therapeutic level for treating retinal degeneration in RC1 dogs. Implants may be an