Topical nerve growth factor attenuates streptozotocin-induced diabetic cataracts via polyol pathway inhibition and Na+/K+-ATPase upregulation

Exp Eye Res. 2021 Jan:202:108319. doi: 10.1016/j.exer.2020.108319. Epub 2020 Oct 17.

Abstract

The purpose of this study was to investigate whether and how topical nerve growth factor (NGF) attenuates streptozotocin (STZ)-induced diabetic cataracts in vivo. Rats were randomly divided into three groups, including the normal control rat group, STZ-induced diabetic cataract rat group (DM group), and STZ-induced diabetic cataract rat group treated with 200 μg/mL recombinant rat β-NGF (DM + NGF group). Cataract formation was evaluated by portable slit lamp biomicroscopy following pupil dilation at 8 weeks. The expression levels of NGF, aldose reductase (AR), and Na+/K+-ATPase in the lens epithelial cells (LECs) of the three groups were measured in the presence or absence of topical NGF. TUNEL-positive LECs were quantified to determine if hyperglycemia caused LEC apoptosis. At 8 weeks, the mean cataract score in the control group was significantly lower than that in DM and DM + NGF groups, and the score in the DM + NGF group was significantly lower than that in the DM group. At the equatorial zone and anterior central zone of lens, NGF and Na+/K+-ATPase expression levels were significantly decreased in the DM group; however, they were partially restored in the DM + NGF group. At the equatorial zone and anterior central zone of lens, AR expression and TUNEL-positive apoptotic LECs were significantly increased in the DM group compared with the control group, however, they were significantly decreased in the DM + NGF group. In conclusion, topical NGF could delay the progression of diabetic cataracts by attenuating polyol pathway activation and increasing Na+/K+-ATPase protein levels.

Keywords: Apoptosis; Diabetic cataract; Nerve growth factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Ophthalmic
  • Animals
  • Apoptosis
  • Cataract / chemically induced
  • Cataract / enzymology
  • Cataract / pathology
  • Cataract / prevention & control*
  • Diabetes Mellitus, Experimental / chemically induced
  • Diabetes Mellitus, Experimental / enzymology
  • Diabetes Mellitus, Experimental / pathology
  • Diabetes Mellitus, Experimental / prevention & control*
  • Hyperglycemia / metabolism
  • In Situ Nick-End Labeling
  • Male
  • Nerve Growth Factor / therapeutic use*
  • Ophthalmic Solutions
  • Polymers
  • Rats
  • Rats, Sprague-Dawley
  • Sodium-Potassium-Exchanging ATPase / metabolism*
  • Streptozocin / toxicity
  • Up-Regulation

Substances

  • Ophthalmic Solutions
  • Polymers
  • polyol
  • Streptozocin
  • Nerve Growth Factor
  • Sodium-Potassium-Exchanging ATPase