Retinal Deficits Precede Cognitive and Motor Deficits in a Rat Model of Type II Diabetes.

Abstract

Purpose:

To investigate the temporal appearance of retinal, cognitive, and motor deficits in Goto-Kakizaki (GK) rats, a spontaneously occurring, polygenic model of type II diabetes. GK rats develop impaired insulin secretion at 2 weeks and fasting hyperglycemia at 4 weeks.

Methods:

In male and female GK rats and Wistar controls, glucose tolerance test (hyperglycemia) and electroretinogram (ERG, retinal function) were performed at 4 and 8 weeks of age. Spectral domain-optical coherence tomography (retinal structure) was assessed at 6 weeks. Spatial alternation (cognitive function) and number of entries (exploratory behavior) were assessed via Y-maze at 4, 5, 6, 7, and 8 weeks. Rotarod (motor function) was performed at 4, 6, and 8 weeks.

Results:

By 4 weeks, the GK rats exhibited significant glucose intolerance (P < 0.001) and retinal deficits, including delays in ERG implicit times (flicker, P < 0.01; oscillatory potentials, P < 0.001). In addition, the GK rats showed greater ERG amplitudes (P < 0.001) and thinner retinas (P < 0.001). At 7 weeks, the GK rats showed deficits in cognitive function (P < 0.001) and exploratory behavior (P < 0.01). However, no motor function deficits were observed by 8 weeks. Interestingly, the male GK rats showed greater hyperglycemia (P < 0.05), but the female rats showed greater ERG delays (P < 0.001).

Conclusions:

In GK rats, retinal function deficits developed prior to cognitive or motor deficits. Future studies will investigate common mechanistic links, long-term functional and vascular changes, and whether early retinal deficits can predict cognitive dysfunction or late-stage retinal disease.

• Authors: Rachael S Allen, Andrew Feola, Cara T Motz, Amy L Ottensmeyer, Kyle C Chesler, Ryan Dunn, Peter M Thulé, Machelle T Pardue
• Journal: Investigative ophthalmology & visual science (Invest Ophthalmol Vis Sci) Vol. 60 Issue 1 Pg. 123-133 (01 02 2019) ISSN: 1552-5783 [Electronic] United States
• PMID: 30640976 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Blood Glucose

Topics

• Animals
• Blood Glucose (metabolism)
• Cognition Disorders (diagnosis, physiopathology)
• Diabetes Mellitus, Type 2 (diagnosis, physiopathology)
• Diabetic Retinopathy (diagnosis, physiopathology)
• Disease Models, Animal
• Electroretinography
• Exploratory Behavior (physiology)
• Female
• Glucose Tolerance Test
• Hyperglycemia (diagnosis, physiopathology)
• Male
• Motor Disorders (diagnosis, physiopathology)
• Rats
• Rats, Mutant Strains
• Rats, Wistar
• Retina (physiopathology)
• Tomography, Optical Coherence