Inhibition of form-deprivation myopia by a GABAAOr receptor antagonist, (1,2,5,6-tetrahydropyridin-4-yl) methylphosphinic acid (TPMPA), in guinea pigs

Graefes Arch Clin Exp Ophthalmol. 2014 Dec;252(12):1939-46. doi: 10.1007/s00417-014-2765-5. Epub 2014 Aug 15.

Abstract

Purpose: To investigate the effects of the relatively selective GABAAOr receptor antagonist (1,2,5,6-tetrahydropyridin-4-yl) methylphosphinic acid (TPMPA) on form-deprivation myopia (FDM) in guinea pigs.

Methods: A diffuser was applied monocularly to 30 guinea pigs from day 10 to 21. The animals were randomized to one of five treatment groups. The deprived eye received daily sub-conjunctival injections of 100 μl TPMPA at a concentration of (i) 0.03 %, ( ii) 0.3 %, or (iii) 1 %, a fourth group (iv) received saline injections, and another (v) no injections. The fellow eye was left untreated. An additional group received no treatment to either eye. Prior to and at the end of the treatment period, refraction and ocular biometry were performed.

Results: Visual deprivation produced relative myopia in all groups (treated versus untreated eyes, P < 0.05). The amount of myopia was significantly affected by the drug treatment (one-way ANOVA, P < 0.0001); myopia was less in deprived eyes receiving either 0.3 % or 1 % TPMPA (saline = -4.38 ± 0.57D, 0.3 % TPMPA = -3.00 ± 0.48D, P < 0.01; 1 % TPMPA = -0.88 ± 0.51D, P < 0.001). The degree of axial elongation was correspondingly less (saline = 0.13 ± 0.02 mm, 0.3 % TPMPA = 0.09 ± 0.01 mm, P < 0.01, 1 % TPMPA = 0.02 ± 0.01 mm, P < 0.001) as was the VC elongation (saline = 0.08 ± 0.01 mm, 0.3 % TPMPA = 0.05 ± 0.01 mm, P < 0.01, 1 % TPMPA = 0.01 ± 0.01 mm; P < 0.001). ACD and LT were not affected (one-way ANOVA, P > 0.05). One percent TPMPA was more effective at inhibiting myopia than 0.3 % (P < 0.01), and 0.03 % did not appreciably inhibit the myopia (0.03 % TPMPA versus saline, P > 0.05).

Conclusions: Sub-conjunctival injections of TPMPA inhibit FDM in guinea pig models in a dose-dependent manner.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axial Length, Eye / drug effects
  • Biometry
  • Disease Models, Animal*
  • Dose-Response Relationship, Drug
  • GABA Antagonists / pharmacology*
  • Guinea Pigs
  • Injections, Intraocular
  • Myopia / etiology
  • Myopia / prevention & control*
  • Phosphinic Acids / pharmacology*
  • Pyridines / pharmacology*
  • Receptors, GABA*
  • Refraction, Ocular / drug effects
  • Sensory Deprivation*

Substances

  • (1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid
  • GABA Antagonists
  • GABA-C receptor
  • Phosphinic Acids
  • Pyridines
  • Receptors, GABA