Clinical intraocular islet transplantation is not a number issue

Abstract

It is now well established that beta cell replacement through pancreatic islet transplantation results in significant improvement in the quality-of-life of type 1 diabetes (T1D) patients. This is achieved through improved control and prevention of severe drops in blood sugar levels. Islet transplant therapy is on the verge of becoming standard-of-care in the USA. Yet, as with other established transplantation therapies, there remain hurdles to overcome to bring islet transplantation to full fruition as a long-lasting therapy of T1D. One of these hurdles is establishing reliable new sites, other than the liver, where durable efficacy and survival of transplanted islets can be achieved. In this article, we discuss the anterior chamber of the eye as a new site for clinical islet transplantation in the treatment of T1D. We specifically focus on the common conceptions, and preconceptions, on the requirements of islet mass, and whether or not the anterior chamber can accommodate sufficient islets to achieve meaningful efficacy and significant impact on hyperglycemia in clinical application.

Keywords: Anterior chamber; Beta cell replacement therapy; Eye; Immune privilege; Intrahepatic; Intraocular; Islet mass; Islet number; Islet transplantation; Liver; Local tolerance; Peripheral tolerance.

Figures

Figure 1

Pancreatic islet transplantation in the eye anterior chamber. (A) Photo of AKITA mouse eye transplanted with 100 IEQ showing islets engrafted on top of the iris individually or in clusters. (B) Longitudinal glycemia (solid lines; left Y axis) and body weight (dashed lines; right Y axis) record of diabetic male AKITA mice (n=4) which were transplanted with 100 IEQ B6 islets. Euglycemia was defined as 3 consecutive blood glucose readings ≤200 mg/dL (dotted line). (C, D) Kaplan-Meyer curves summarizing the % normoglycemic mice (expressed as “diabetes reversal rate”) following transplantation in (C) AKITA (n=4) and (D) B6 recipients (n=2 for 75 IEQ and n=3 for 150, 300, and 500 IEQ groups).