Abstract
Purpose: :
Radiation (RTx) causes dry eye (DE) and dry mouth and as in other sicca syndromes they are incurable. The aims of this work are: a) to evaluate a mouse model of DE induced by equivalent of human therapeutic levels of radiation, b) to investigate the mechanisms and c) to evaluate the protective effect of gene therapy with adenovirus encoding human erythropoietin gene, AdLTR2EF1a-hEPO (AdEpo).
Methods: :
C3H female mice were submitted to 5 sessions of RTx, with prior salivary cannulation of AdEPO or not and compared with naïve controls at day 10 and week 8 of RTx treatment initiation. The main outcomes were tear secretion (phenol red thread), lacrimal gland (LG) weight, hematocrit and markers of inflammation, micro vessels and oxidative damage.
Results: :
The body and LG weight was significant lower in RTx groups compared to control at day 10 (p=0.0001 and 0.02, respectively). Tear secretion was also reduced in both groups by day 10, compared to controls (p<0.0001) and it was sustained along the whole observational period, but recovered in AdEpo+RTx (p=0.0003). Human Epo hormone protein and DNA were not significantly higher in AdEpo+RTx LG. Hematocrit was significantly higher in AdEpo+RTx at day 10 and week 8 (p=0.0079 and 0.0084, respectively). Cornea epithelia were significantly thinner at day 10 in RTx compared to control and AdEpo+RTx group (p<0.0001). The major change observed in LG was a significant reduction in VEGF-R2, marker of micro vessels in RTx group, that were prevented in AdEpo+RTx group (p=0.03).
Conclusions: :
The present work reveals that RTx is able to induce DE in mice. The mechanism involves reduction in micro vessels. AdEPO gene therapy protected cornea epithelia and recovered LG function. Those effects are due to systemic Epo, since it was not over expressed in LG.
Keywords: cornea: epithelium • gene transfer/gene therapy • cornea: tears/tear film/dry eye