Forskolin eye drops improve retinal damage from ischemia/reperfusion

Mol Vis. 2021 May 21:27:365-369. eCollection 2021.

Abstract

Purpose: To determine whether forskolin, a protein kinase A (PKA) agonist, eye drops could reduce neuronal and vascular damage after exposure to ischemia/reperfusion (I/R).

Methods: C57BL/6J mice were exposed to the I/R protocol. A group of mice were given forskolin eye drops (10 μM) daily. Two days after I/R, neuronal measurements were performed, while vascular measurements were performed at 10 days post-I/R. Western blotting was conducted to investigate whether forskolin could increase PKA levels and reduce the levels of inflammatory mediators.

Results: Forskolin statistically significantly increased PKA levels, but not exchange protein activated by cAMP 1 (Epac1). The forskolin eye drops also reduced neuronal and vascular damage compared to I/R alone. Tumor necrosis factor alpha (TNF-α) and interleukin-1-β (IL-1β) levels were statistically significantly reduced after administration of forskolin eye drops compared to I/R alone.

Conclusions: Forskolin eye drops were protective against I/R. The findings offer a new therapeutic for local delivery.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Ophthalmic
  • Animals
  • Blotting, Western
  • Cell Count
  • Colforsin / administration & dosage*
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • Interleukin-1beta / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Ophthalmic Solutions
  • Reperfusion Injury / complications
  • Reperfusion Injury / drug therapy*
  • Reperfusion Injury / enzymology
  • Retinal Diseases / drug therapy*
  • Retinal Diseases / enzymology
  • Retinal Diseases / etiology
  • Retinal Vessels / pathology
  • Tumor Necrosis Factor-alpha / metabolism
  • Vasodilator Agents / administration & dosage*

Substances

  • Interleukin-1beta
  • Ophthalmic Solutions
  • Tumor Necrosis Factor-alpha
  • Vasodilator Agents
  • Colforsin
  • Cyclic AMP-Dependent Protein Kinases