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Sustained insulin release in a model of diabetic retinopathy (DR) rescues retinal cells from apoptotic cell death

Early stage research, conducted at the Department of Ophthalmology, Pennsylvania State University, has indicated that hydrogel discs loaded with insulin lispro and inserted sub-conjunctivally, may provide therapeutic benefit in diabetic retinopathy (DR). The hydrogel inserts, shown to be capable of sustained drug release for up to 5 months, appeared to be safe and non-toxic. According to the research team, diabetic animals treated with hydrogel-insulin inserts had significantly reduced DNA fragmentation in retinal cells, a proxy marker for cellular apoptosis. If capable of robust reproduction in human subjects the technology could provide transformative treatments for DR patients.


The increasing incidence of diabetes, with the concomitant increase in diabetic co-morbidities, such as diabetic retinopathy, is causing significant public health challenges globally. Of the estimated 29 million diabetic patients in the US, almost 15% between the ages of 20 and 74 years may suffer DR. While a number of treatment strategies exist, the Pennsylvania State University research team had focused on developing approaches to rescue retinal neuronal cells from degeneration in order to preserve as much visual function as possible. While eye drops and injections are used commonly in clinical practice, risks persist regarding patient compliance and infection, respectively. As a result, an opportunity to provide a single implant capable of facilitating slow release drug delivery over a sustained period of time might offer significant advantages over current standard of care.


Freeze dried hydrogel discs (2 mm in diameter and 1.6 mm in height) incorporating insulin were synthesized by UV photopolymerization of N-isopropylacrylamide and a dextran macromere containing oligolactate-(2-hydroxyetheyl methacrylate). The discs were subconjunctivally inserted into the eyes of type 1 diabetic animal models. Two time points at 2 days and 1 week post implantation were assessed to quantify the treatment effect by analyzing the level of fragmented retinal DNA. The researchers found that after insulin lispro-loaded hydrogels were implanted in diabetic animals, the retinal DNA fragmentation in treated eyes was “significantly reduced by approximately half.” According to the researchers, the results indicated that the insulin-loaded hydrogel inserts were able to rescue retinal cells from apoptosis for at least 1 week, suggesting potential benefit from the slow release of insulin lispro. While the number of models used was low, the results provide a positive indication for potential human use if significant enough results can be reproduced in a human clinical study. The researchers concluded their study stating that, “all these results suggest that the developed hydrogels have potential to sustain release of low-dose biologically active insulin to the retina via subconjunctival implantation to minimize DR without the risk of hypoglycemia.”