Histological effect and protein expression in subthreshold transpupillary thermotherapy in rabbit eyes.
OBJECTIVE
To investigate the histological effect of subthreshold transpupillary thermotherapy (TTT) on the retina.


METHODS
We performed TTT in normal pigmented rabbit eyes using an 810-nm diode laser with spot size of 1.2 mm, power of 50 mW, and varying durations of 15, 30, or 60 seconds. Four weeks later, fluorescein angiography was performed, and the enucleated eyes were examined by means of electron microscopy and immunohistochemical staining.


RESULTS
Funduscopy immediately and at 4 weeks showed no discernable changes at TTT sites, and fluorescein angiography at 4 weeks showed no abnormalities. However, electron microscopy showed photoreceptor and retinal pigment epithelium cell disruption, changes more prominent with longer durations of treatment. Immunohistochemical staining was positive for heat shock protein 60, heat shock protein 70, tumor necrosis factor alpha, and vascular cell adhesion molecule 1 in the photoreceptors and retinal pigment epithelium at TTT sites. Untreated control eyes showed no staining.


CONCLUSIONS
Despite the absence of changes evident by funduscopy and fluorescein angiography, TTT resulted in dose-dependent histological changes in photoreceptors and retinal pigment epithelium. The induction of heat shock proteins, cytokines, and cell adhesion molecules may play a role in the tissue response to subthreshold TTT. Clinical Relevance Unrecognized damage to the retina and retinal pigment epithelium may contribute to visual loss in eyes that undergo subthreshold TTT.
Department of Ophthalmology, Kyorin University School of Medicine, Mitaka-shi, Tokyo, Japan.
Yoshihiro
Y
Morimura
Annabelle A
AA
Okada
Atsushi
A
Hayashi
Sayuri
S
Fujioka
Noriyasu
N
Hashida
Sumie
S
Kawahara
Tetsuo
T
Hida
D000818:Animals; D018834:Chaperonin 60 / Q000378:metabolism; D005451:Fluorescein Angiography; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006979:Hyperthermia, Induced / Q000009:adverse effects* / Q000379:methods; D007150:Immunohistochemistry; D028022:Low-Level Light Therapy / Q000379:methods*; D008854:Microscopy, Electron; D019721:Ophthalmoscopes; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D010857:Pigment Epithelium of Eye / Q000473:pathology*; D011817:Rabbits; D012160:Retina / Q000378:metabolism* / Q000473:pathology*; D012171:Retinal Vessels; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D018834:Chaperonin 60; D018840:HSP70 Heat-Shock Proteins; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1