Protracted Vascular Retinopathy in a Novel Model of Spontaneous Type 2 Diabetes

  • Author / Creator
    Gotzmann, Jonathan D.
  • Diabetic retinopathy (DR) is the leading cause of blindness in working aged adults, however lack of a suitable animal model has limited our understanding of the disease. The Nile grass rat (NR) is a cone-rich crepuscular rodent that spontaneously develops hyperglycemia (HG) when fed standard lab chow, making them a candidate to study the effects of HG on the retina. Vascular integrity was assessed in two groups of NRs at 6, 12 and 18 months of age: 1) standard lab chow: fed Prolab 2000 (HG); 2) low calorie, high fiber diet: fed Mazuri Chinchilla (control). Results revealed many classic hallmarks of human DR, such as pericyte loss, degeneration of capillaries and microaneurysm formation. Furthermore, early cataract development was seen in hyperglycemic NRs, as early as 12 months of age. In addition to the classic vascular changes associated with DR, differences in inner retinal circuitry were investigated. Hyperglycemic NRs showed a decreased ability for age-related dendritic sprouting specific to dopaminergic amacrine cells and also a marked reduction of connexin 36 (Cx36) expression in the outer plexiform layer (OPL) and inner plexiform layer (IPL). Together, our results demonstrate that NRs recapitulate the key pathological features and slow time course of early human DR. Therefore, NRs provide a unique opportunity to study the pathogenesis of DR as well as providing new understanding to the changes of the diabetic retina.

  • Subjects / Keywords
  • Graduation date
  • Type of Item
  • Degree
    Master of Science
  • DOI
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.
  • Language
  • Institution
    University of Alberta
  • Degree level
  • Department
    • Department of Physiology
  • Supervisor / co-supervisor and their department(s)
    • Sauve, Yves (Ophthalmology and Visual Sciences)
  • Examining committee members and their departments
    • Allison, William (Biological Sciences)
    • Chan, Catherine (Physiology)
    • Sauve, Yves (Ophthalmology and Visual Sciences)
    • MacDonald, Patrick (Pharmacology)
    • Nguyen, Peter (Physiology)