Insulin-like growth factor-2 antisense oligonucleotides inhibits myopia by expression blocking of retinal insulin-like growth factor-2 in guinea pig

Clin Exp Ophthalmol. 2012 Jul;40(5):503-11. doi: 10.1111/j.1442-9071.2011.02683.x. Epub 2011 Nov 4.

Abstract

Objective: To clarify the role of IGF-2 on the development of myopia, the dynamic expression of IGF-2 was investigated in the FD eyes' retina, and the effects of intravitreous injection with IGF-2 ASON was studied on the diopter and axial eye length of FD eyes.

Methods: 64 guinea pigs were divided into 2 groups. In group A (n = 24), the right eyes were covered. On days 7, 14 and 21, the diopter, axial eye length and level of IGF-2 of both eyes were measured in every 8 guinea pigs. In group B (n = 40), the right eyes were covered. On day 1, the right eyes were received intravitreal injection with 40 µg IGF-2SON, 10 µg, 20 µg or 40 µg IGF-2 ASON. The diopter, axial eye length and level of IGF-2 were measured on day 14.

Results: FD eyes showed myopic shift, axial length enlongation, and up-regulation in retinal IGF-2 from day 7 to day 21. The level of retinal IGF-2 in FD eyes was higher than that in non-FD eyes. Compare with FD eyes without injection, the myopia diopter of FD eyes decreased in received intravitreous injection with IGF-2 ASON, axial length shortened, and down-regulated with retinal IGF-2. With the increase dose of IGF-2 ASON, the change of myopic diopter, axial length, and level of retinal IGF-2 were showed more and more significant.

Conclusions: FD is effective to up-regulate the level of retinal IGF-2 expression in guinea pig. Intravitreous injection with IGF-2 ASON can inhibit the development of myopia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axial Length, Eye
  • Blotting, Western
  • Disease Models, Animal*
  • Gene Expression Regulation / drug effects*
  • Guinea Pigs
  • Insulin-Like Growth Factor II / genetics*
  • Intravitreal Injections
  • Liposomes
  • Myopia / metabolism
  • Myopia / prevention & control*
  • Oligonucleotides, Antisense / administration & dosage*
  • RNA, Messenger / metabolism
  • Retina / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Up-Regulation

Substances

  • Liposomes
  • Oligonucleotides, Antisense
  • RNA, Messenger
  • Insulin-Like Growth Factor II