Long-term effect of therapeutic laser photocoagulation on gene expression in the eye.
Microarray-based gene expression analysis demonstrated that laser photocoagulation (LPC) of mouse eyes had a long-term effect on the expression of genes functionally related to tissue repair, cell migration, proliferation, ion, protein and nucleic acid metabolism, cell signaling, and angiogenesis. Six structural genes, including five crystallins (Cryaa, Cryba1, Crybb2, Crygc, Crygs) and keratin 1-12 (Krt1-12), the anti-angiogenic factor thrombospondin 1 (Tsp1), the retina- and brain-specific putative transcription factor tubby-like protein 1 (Tulp1), and transketolase (Tkt), a key enzyme in the pentose-phosphate pathway, were all shown to be up-regulated by real-time PCR and/or Western blotting. Immunohistochemistry localized five of these proteins to the laser lesions and surrounding tissue within the retina and pigmented epithelium. This is the first study demonstrating long-term changes in the expression of these genes associated with LPC. Therefore, it suggests that modulated gene expression might contribute to the long-term inhibitory effect of LPC. In addition, these genes present novel targets for gene-based therapies aimed at treating microangiopathies, especially diabetic retinopathy, a disease currently only treatable with LPC.
Binz
Nicolette
N
Molecular Ophthalmology, Lions Eye Institute, Nedlands, Australia. binz@cyllene.uwa.edu.au
Graham
Caroline E
CE
Simpson
Ken
K
Lai
Yvonne K Y
YK
Shen
Wei-Yong
WY
Lai
Chooi-May
CM
Speed
Terence P
TP
Rakoczy
P Elizabeth
PE
D000818:Animals; D005136:Eye Proteins / Q000235:genetics* / Q000378:metabolism / Q000528:radiation effects*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000528:radiation effects*; D017075:Laser Coagulation; D051379:Mice; D008810:Mice, Inbred C57BL; D010857:Pigment Epithelium of Eye / Q000378:metabolism / Q000528:radiation effects; D012160:Retina / Q000378:metabolism / Q000528:radiation effects; D013997:Time Factors
D005136:Eye Proteins