Contribution of ROCK in contraction of trabecular meshwork

Proposed mechanism for regulating aqueous outflow in monkey and human eyes

Emi Nakajima, Takeshi Nakajima, Yoko Minagawa, Thomas (Tom) Shearer, Mitsuyoshi Azuma

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

Aqueous outflow in the conventional outflow pathway is regulated by the contraction and relaxation of the ciliary muscle (CM) and the trabecular meshwork (TM). Rho-associated coiled coil-forming protein kinase (ROCK) is thought to regulate actomyosin-based contractility in many types of cells by phosphorylation of ROCK substrates. In animal models, ROCK inhibitor Y-39983 relaxed CM and TM and decreased intraocular pressure (IOP). Thus, ROCK is implicated in the regulation of aqueous outflow and IOP. However, the site of action of ROCK in monkey and man is unknown. In the present communication, RT-PCR analysis of monkey tissues showed higher levels of mRNAs for ROCK and ROCK substrates in TM compared to CM. Human TM also showed higher levels of mRNAs for ROCK and ROCK substrates compared to CM. Differences between TM and CM in human were not as high as in monkey. ROCK inhibitor Y-39983 led to a dose-dependent relaxation of carbachol-induced, contracted TM from monkey. In contrast, Y-39983 was only slightly effective in relaxing CM. Our results suggested that TM was one of the major sites for regulating IOP by ROCK. ROCK inhibitor Y-39983 might be a candidate drug for lowering IOP by increasing conventional outflow and producing fewer side effects on accommodation and miosis.

Original languageEnglish (US)
Pages (from-to)701-708
Number of pages8
JournalJournal of Pharmaceutical Sciences
Volume94
Issue number4
DOIs
StatePublished - Apr 2005

Fingerprint

Trabecular Meshwork
Haplorhini
Muscle
Intraocular Pressure
Muscles
Substrates
Actomyosin
rho-Associated Kinases
Messenger RNA
Phosphorylation
Miosis
Carbachol
Muscle Relaxation
Animals
Tissue
Animal Models
Y-39983
Communication
Polymerase Chain Reaction
Pharmaceutical Preparations

Keywords

  • Ciliary muscle
  • Contraction
  • GeneChip array
  • Myosin phosphatase
  • Rho-associated coiled coil-forming protein kinase (ROCK)
  • ROCK inhibitor Y-39983
  • RT-PCR
  • Trabecular meshwork

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Chemistry(all)
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science

Cite this

Contribution of ROCK in contraction of trabecular meshwork : Proposed mechanism for regulating aqueous outflow in monkey and human eyes. / Nakajima, Emi; Nakajima, Takeshi; Minagawa, Yoko; Shearer, Thomas (Tom); Azuma, Mitsuyoshi.

In: Journal of Pharmaceutical Sciences, Vol. 94, No. 4, 04.2005, p. 701-708.

Research output: Contribution to journalArticle

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