Upregulation of neurotrophic factor-related gene expression in retina with experimental autoimmune uveoretinitis by intravitreal injection of tacrolimus (FK506).
OBJECTIVE
The current study was designed to determine whether intravitreal injection of tacrolimus (FK506) modulates the gene expression of neurotrophic factor-related molecules in the retina from eyes with induced experimental autoimmune uveoretinitis (EAU) in rats.


METHODS
Rats were immunised with interphotoreceptor retinoid binding protein peptide (R14) and given intravitreal injection of tacrolimus on day 12 after immunisation. As control, immunised rats received intravitreal injection of vehicle. On day 15 after immunisation, changes in the genetic programme associated with neuroprotection and inflammatory responses in the retinas from both groups were determined by DNA microarray analyses and confirmed by real-time PCR analyses.


RESULTS
The gene expression of inflammatory responses was markedly reduced in tacrolimus-treated eyes. Genes for molecules associated with neuroprotection (oestrogen receptor, erythropoietin receptor, gamma-aminobutyric acid receptor, protein kinase C, glial cell line-derived neurotrophic factor receptor, fibroblast growth factor and neuropeptide Y receptor) were upregulated in the retinas from tacrolimus-treated eyes.


CONCLUSIONS
Intravitreal injection of tacrolimus modulated the genes related to neuroprotection in the retina during the ongoing process of EAU. This treatment may be useful for the neuroprotection of retina with severe uveitis as well as for immunosuppression in the uveitic eyes.
Oh-i
Keiko
K
Department of Ophthalmology, Tokyo Medical University, 6-7-1, Nishi-shinjuku, Shinjuku-ku, Tokyo, Japan 160-0023.
Keino
Hiroshi
H
Goto
Hiroshi
H
Yamakawa
Naoyuki
N
Takeuchi
Masaru
M
Usui
Masahiko
M
Iwasaki
Takuya
T
D000818:Animals; D001327:Autoimmune Diseases / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology; D007267:Injections; D009414:Nerve Growth Factors / Q000096:biosynthesis* / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011917:Rats, Inbred Lew; D012173:Retinitis / Q000378:metabolism*; D016559:Tacrolimus / Q000008:administration & dosage / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects*; D014606:Uveitis, Anterior / Q000378:metabolism*; D014822:Vitreous Body
D007166:Immunosuppressive Agents; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D016559:Tacrolimus