title: Fibrotic disorders in the eye: targets of gene therapy.
abstract: Fibrotic diseases, e.g., cutaneous and corneal scarring, keloids, and liver and lung fibrosis, etc., are characterized by appearance of myofibroblasts, the key player of the fibrogenic reaction, and excess accumulation of extracellular matrix with resultant tissue contraction and impaired functions. Inflammatory/fibrogenic growth factors/cytokines produced by injured tissues play a pivotal role in fibrotic tissue formation. Ocular tissues are also susceptible to fibrotic diseases. In this article, the pathogenesis of such fibrotic disorders in the eye, i.e., scarring in the cornea and conjunctiva, post-cataract surgery fibrosis of the lens capsule and proliferative vitreoretinopathy are reviewed. Focus is put on the roles of myofibroblast and signals activated by the fibrogenic cytokine, transforming growth factor beta. Modulation of signal transduction molecules, e.g., Smad and mitogen-activated protein kinases, by gene transfer and other technology is beneficial and can be an important treatment regiment to overcome (prevent or treat) these diseases.
authors.affiliation: Department of Ophthalmology, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-0012, Japan. shizuya@wakayama-med.ac.jp
authors.forename: Shizuya
authors.initials: S
authors.lastname: Saika
authors.forename: Osamu
authors.initials: O
authors.lastname: Yamanaka
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Sumioka
authors.forename: Takeshi
authors.initials: T
authors.lastname: Miyamoto
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Miyazaki
authors.forename: Yuka
authors.initials: Y
authors.lastname: Okada
authors.forename: Ai
authors.initials: A
authors.lastname: Kitano
authors.forename: Kumi
authors.initials: K
authors.lastname: Shirai
authors.forename: Sai-ichi
authors.initials: S
authors.lastname: Tanaka
authors.forename: Kazuo
authors.initials: K
authors.lastname: Ikeda
mesh_terms: D000818:Animals; D003228:Conjunctiva / Q000473:pathology*; D003315:Cornea / Q000473:pathology*; D005128:Eye Diseases / Q000473:pathology / Q000628:therapy*; D005347:Fibroblasts / Q000473:pathology; D005355:Fibrosis / Q000628:therapy; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D007903:Lens Capsule, Crystalline / Q000473:pathology*; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics; D012160:Retina / Q000473:pathology*; D012867:Skin / Q000473:pathology; D051785:Smad Proteins / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics
chemical_list: D051785:Smad Proteins; D016212:Transforming Growth Factor beta; D020928:Mitogen-Activated Protein Kinases