TY - JOUR
T1 - Effect of sustained insulin-releasing device made of poly(ethylene glycol) dimethacrylates on retinal function in streptozotocin-induced diabetic rats
AU - Hoshi, Ayako
AU - Nagai, Nobuhiro
AU - Daigaku, Reiko
AU - Motoyama, Remi
AU - Saijo, Saaya
AU - Kaji, Hirokazu
AU - Abe, Toshiaki
N1 - Funding Information:
This study was supported by a Basic Science and Platform Technology Program for Innovative Biological Medicine, from the Japan Agency for Medical Research and Development (AMED), Japan, and the Business Incubation Program (BIP), from Tohoku University, Japan.
Publisher Copyright:
© 2020, Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2020/6/1
Y1 - 2020/6/1
N2 - In this study, we developed a subcutaneous insulin-releasing device consisting of a disk-shaped capsule and drug formulation comprised of poly(ethylene glycol) dimethacrylates, then evaluated its efficacy on retinal function in streptozotocin (STZ)-induced diabetic rats. In vitro release studies showed that recombinant human insulin was released with a constant rate for more than 30 days. The device was able to maintain a basal level of blood glucose in diabetic rats for a prolonged period of more than 30 days, simultaneously preventing a decrease in body weight. For assessing the pharmacological effect of the device on retinal function in diabetic rats, electroretinograms were conducted for 12 weeks. The reduction in amplitude and delay in implicit time were attenuated by the device during the initial 4 weeks of application. The increase in gene expression of protein kinase C (PKC)-γ and caspase-3 in the diabetic retina was also attenuated by the device. Immunohistochemistry showed that the increase in glial fibrillary acidic protein expression in the diabetic retina was attenuated by the device. Histological evaluation of subcutaneous tissue around the device showed the biocompatibility of the device. In conclusion, the insulin-releasing device attenuated the reduction of retinal function in STZ-induced diabetic conditions for 4 weeks and the efficacy of the device might be partially related to PKC signaling in the retina. The long-term ability to control the blood glucose level might help to reduce the daily frequency of insulin injections. [Figure not available: see fulltext.]
AB - In this study, we developed a subcutaneous insulin-releasing device consisting of a disk-shaped capsule and drug formulation comprised of poly(ethylene glycol) dimethacrylates, then evaluated its efficacy on retinal function in streptozotocin (STZ)-induced diabetic rats. In vitro release studies showed that recombinant human insulin was released with a constant rate for more than 30 days. The device was able to maintain a basal level of blood glucose in diabetic rats for a prolonged period of more than 30 days, simultaneously preventing a decrease in body weight. For assessing the pharmacological effect of the device on retinal function in diabetic rats, electroretinograms were conducted for 12 weeks. The reduction in amplitude and delay in implicit time were attenuated by the device during the initial 4 weeks of application. The increase in gene expression of protein kinase C (PKC)-γ and caspase-3 in the diabetic retina was also attenuated by the device. Immunohistochemistry showed that the increase in glial fibrillary acidic protein expression in the diabetic retina was attenuated by the device. Histological evaluation of subcutaneous tissue around the device showed the biocompatibility of the device. In conclusion, the insulin-releasing device attenuated the reduction of retinal function in STZ-induced diabetic conditions for 4 weeks and the efficacy of the device might be partially related to PKC signaling in the retina. The long-term ability to control the blood glucose level might help to reduce the daily frequency of insulin injections. [Figure not available: see fulltext.]
UR - http://www.scopus.com/inward/record.url?scp=85085271613&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85085271613&partnerID=8YFLogxK
U2 - 10.1007/s10856-020-06392-8
DO - 10.1007/s10856-020-06392-8
M3 - Article
C2 - 32462459
AN - SCOPUS:85085271613
SN - 0957-4530
VL - 31
JO - Journal of Materials Science: Materials in Medicine
JF - Journal of Materials Science: Materials in Medicine
IS - 6
M1 - 52
ER -
