Islet transplantation to the anterior chamber of the eye - a future treatment option for insulin-deficient type-2 diabetics? A case report from a nonhuman type-2 diabetic primate

Autor: Martin Köhler, Xiaofeng Zheng, Yusuf Ali, Per Olof Berggren, Sai Bo Bo Tun, Lisa Juntti-Berggren, Minni Chua, Midhat H. Abdulreda, Veluchamy A Barathi, Riasat Hasan
Přispěvatelé: Lee Kong Chian School of Medicine (LKCMedicine)
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Intraocular pressure
medicine.medical_treatment
Insulins
Islets of Langerhans Transplantation
lcsh:Medicine
diet-induced type-2 diabetes
intraocular transplant
chemistry.chemical_compound
0302 clinical medicine
anterior chamber of the eye
Insulin-Secreting Cells
Medicine
Glucose homeostasis
geography.geographical_feature_category
Islet Transplantation
Islet
Fructosamine
medicine.anatomical_structure
Original Article
medicine.medical_specialty
endocrine system
Anterior Chamber
nonhuman primates
Biomedical Engineering
030209 endocrinology & metabolism
Diabetes Mellitus
Experimental
03 medical and health sciences
Islets of Langerhans
Internal medicine
Diabetes mellitus
Animals
Medicine [Science]
Transplantation
geography
business.industry
Nonhuman Primates
Pancreatic islets
Insulin
islet transplantation
lcsh:R
Cell Biology
medicine.disease
Macaca fascicularis
030104 developmental biology
Endocrinology
Diabetes Mellitus
Type 1
chemistry
Diabetes Mellitus
Type 2
business
Zdroj: Cell Transplantation, Vol 29 (2020)
Cell Transplantation
Popis: Replacement of the insulin-secreting beta cells through transplantation of pancreatic islets to the liver is a promising treatment for type-1 diabetes. However, low oxygen tension, shear stress, and the induction of inflammation lead to significant islet dysfunction and loss. The anterior chamber of the eye (ACE) has gained considerable interest and represents an alternative therapeutic islet transplantation site because of its accessibility, high oxygen tension, and immune-privileged milieu. We have previously demonstrated the feasibility of intraocular islet transplant in mouse and nonhuman primate models of type-1 diabetes and are now assessing its efficacy on glucose homeostasis in a nonhuman primate model of type-2 diabetes. We transplanted allogeneic donor islets (1,500 islet equivalents/kg) into the anterior chamber of one eye in a cynomolgus monkey with high-fat-diet-induced type-2 diabetes. Repeated examinations of the anterior and posterior segments of both eyes were done to monitor the engrafted islets and assess the overall ocular health. Fasting blood glucose level, blood biochemistry, and other metabolic parameters were routinely evaluated to determine the function of the islet graft and diabetes status. The transplanted islets were rapidly engrafted onto the iris and became vascularized 1 month after transplantation. We did not detect changes in intraocular pressure, cataract formation, ophthalmitis, or retinal vessel deformation. A significant lower fasting blood glucose level was observed while the graft was in place, and the transplantation reverts the progression of diabetes. The metabolic markers, hemoglobin A1C and fructosamine, demonstrated improvement following islet transplantation. As a conclusion, intraocular islet transplantation in one eye of a cynomolgus monkey with type-2 diabetes improved its overall plasma glucose homeostasis, as evidenced by short-term measures and long-term metabolic markers. These results further support the future application of the ACE as an alternative site for clinical islet transplants in the context of type-2 diabetes. Nanyang Technological University National Medical Research Council (NMRC) Published version We thank Dr. Bryan Ogden and the veterinary team from SingHealth Experimental Medicine Centre (SEMC) for the husbandry care and handling of the animals. We appreciate the advice and input of Dr. Hla Myat Htoon from Singapore Eye Research Institute (SERI) on the statistical analysis. The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by a Lee Kong Chian School of Medicine, Nanyang Technological University start-up grant M4230003 (to P-OB), Lee Kong Chian School of Medicine, Nanyang Technological University Bridging Assistant Grants 4, the Lee Foundation Grant 2015 granted by SingHealth Transplant. VAB was supported by NMRC/CG-INCEPTOR/Pre-Clinical Core Platform/2017_SERI. P-OB was also supported by the Swedish Research Council, the Family Erling-Persson Foundation, the Stichting af Jochnick Foundation, the Scandia Insurance Company Limited, and the Diabetes Research and Wellness Foundation. Article processing charge was supported by National Medical Research Council (NMRC/CG/C010A-PreClinical/2017) of Singapore.
Databáze: OpenAIRE
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