Retinal Astrocytes and Microglia Activation in Diabetic Retinopathy Rhesus Monkey Models

ABSTRACT

Purpose

To assess the retinal neurodegeneration in type-1 diabetes mellitus (T1DM) and type-2 diabetes mellitus (T2DM) rhesus monkeys, and to investigate whether alterations of glial cells occur in the early stage of diabetic retinopathy (DR).

Materials and methods

T1DM rhesus monkeys were established by daily intravenous injections of streptozotocin (STZ, 25 mg/kg body weight) in citrate buffer (pH 4.5) for 5 days, while T2DM rhesus monkeys were induced by feeding with high-fat diet. The period of DR in rhesus monkeys was evaluated by fundoscopy and optical coherence tomography (OCT). Afterward, the morphological changes of inner neurons and glial cells in the retina were detected by immunofluorescence (IF).

Results

When compared with the control groups, no difference was observed in both T1DM and T2DM by fundus photographs, while slight exudation and effusion in the blood vessels of retina of rhesus monkeys were found by OCT in DM rhesus monkeys. In addition, the expression of glial fibrillary acidic protein (GFAP) and ionized calcium-binding adaptor molecule (Iba1) were significantly increased in both T1DM (P < .01) and T2DM (P < .05) rhesus monkeys. Moreover, the positive expression of PKC-α, parvalbumin, and NeuN were significantly decreased, while the positive expression of calbindin showed no difference in T1DM group. However, only the expression cells of PKC-α were reduced in T2DM group when compared with that of the control group.

Conclusion

Astrocytes activation, reactive gliosis, and neurodegeneration were observed in both T1DM and T2DM rhesus monkey models at the early stage of DR.

KEYWORDS:

• Rhesus monkeys
• diabetic retinopathy
• astrocytes activation
• reactive gliosis
• neurodegeneration

Data availability statement

The data that support the findings of this study are available from the corresponding author (Z.L.C) by request.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Authors’ contributions

Y.X, Q.H.L and J.F.C designed the experiments and interpreted the data. W.T.L and Y.X executed a part of experiments. C.H, Asad Jahangir and Q.H.L revised the article critically for intellectual content. Z.L.C supervised the project.

Additional information

Funding

The present study was supported by Sichuan International Science and Technology Innovation Cooperation Project [2020YFH0148] and the basic research program of Sci-tech department of Sichuan Province [2019YJ0426].