Fibrotic disorders in the eye: targets of gene therapy.
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.
Saika
Shizuya
S
Department of Ophthalmology, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-0012, Japan. shizuya@wakayama-med.ac.jp
Yamanaka
Osamu
O
Sumioka
Takayoshi
T
Miyamoto
Takeshi
T
Miyazaki
Ken-ichi
K
Okada
Yuka
Y
Kitano
Ai
A
Shirai
Kumi
K
Tanaka
Sai-ichi
S
Ikeda
Kazuo
K
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
D051785:Smad Proteins; D016212:Transforming Growth Factor beta; D020928:Mitogen-Activated Protein Kinases