Effects of endothelin-1 eyedrops on the retina in rats

J Cardiovasc Pharmacol. 2004 Nov:44 Suppl 1:S421-5. doi: 10.1097/01.fjc.0000166286.85785.a1.

Abstract

Eye disorder accompanied with chronic retinal microvascular obstruction, such as diabetic retinopathy, exists in many diseases. However, it is difficult to produce this model experimentally in the animal eye. Endothelin-1 eyedrops were prepared in order to examine whether the eyedrops affect the rat retina and whether we can produce an obstruction model. Endothelin-1 eyedrops diluted by artificial tears in seven stages from 4 x 10(-5) M to 4 x 10(-11) M were arranged. We administered this solution three times a day in the left eye of male Sprague-Dawley rats. Artificial tears alone were applied to the right eye as a control vehicle. After 2 weeks, rats were sacrificed under anesthesia and the retinal tissues were isolated. As an index to the action of endothelin- 1 eyedrops to the retina, the expressions of endothelin-A (ETA) and endothelin-B (ETB) receptors in the retina were compared in both eyes. Frozen sections of the retina were immunostained to reveal the distribution of the ETA and ETB receptors. We also examined ETA and ETB mRNA expression by quantitative real-time polymerase chain reaction. As a result, the expressions of ETA and ETB receptors are reduced with both immunostaining and the mRNA levels in the left eye, in which endothelin-1 eyedrops were applied at 4 x 10(-5) M. It is suggested that endothelin-1 eyedrops affected the retina and the possibility of producing the experimental model of chronic microvascular obstruction in the rat retina.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Topical
  • Animals
  • Down-Regulation
  • Endothelin-1 / administration & dosage
  • Endothelin-1 / toxicity*
  • Immunohistochemistry
  • Male
  • Ophthalmic Solutions
  • Polymerase Chain Reaction
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Endothelin A / genetics
  • Receptor, Endothelin A / metabolism*
  • Receptor, Endothelin B / genetics
  • Receptor, Endothelin B / metabolism*
  • Retina / drug effects*
  • Retina / metabolism
  • Retina / pathology
  • Retinal Diseases / chemically induced*
  • Retinal Diseases / metabolism
  • Retinal Diseases / pathology

Substances

  • Endothelin-1
  • Ophthalmic Solutions
  • RNA, Messenger
  • Receptor, Endothelin A
  • Receptor, Endothelin B