The Effect of Everolimus on Scar Formation in Glaucoma Filtering Surgery in a Rabbit Model.
To investigate the efficiency of everolimus on the prevention of postoperative scar in a rabbit model of glaucoma filtering surgery in comparison with mitomycin-C (MMC).



Thirty New Zealand albino rabbits were randomly assigned into 3 groups, each including ten rabbits: an everolimus group (Group 1), a MMC group (Group 2), and a sham group (Group 3). A limbal-based trabeculectomy was performed on the right eyes of all the rabbits. For 28 days following surgery, the eyes were evaluated in terms of intraocular pressure (IOP), morphological and biomicroscopic changes, and complications in the bleb. On the 28th day, four eyes randomized from each group were enucleated and histologically and immunohistochemically analyzed. Transforming growth factor-β1 (TGF-β1), metalloproteinase (MMP-2, MMP-9), and proliferative cell nuclear antigen (PCNA) expressions in each group were evaluated. The terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) method was used for apoptosis.



Bleb survival was statistically significantly longer for a period in Group 1 compared to Group 2. When postoperative IOPs of three groups were measured, it was seen that there is significant IOP reduction in all three groups. However, there were increases in the mean IOP values beginning from the 5th day in Group 2 and from the 3rd day in Group 3 while in Group 1 mean IOP values began to increase beginning from 10th day and the mean IOP values in Group 1 remained at a lower level in comparison to the other groups for 28 days (p < 0.05). The expressions of TGF-β1, MMP-2, MMP-9, and PCNA were reduced in Group 1 compared to other groups. TUNEL positive apoptotic cells were significantly increased in Group 1 compared to other groups (p < 0.05).



Everolimus appears to suppress the proliferation of fibroblast and thus may provide an effective treatment strategy in glaucoma filtering surgery.
a Department of Ophthalmology , Diyarbakir Bismil State Hospital , Diyarbakir , Turkey.
Ruken
R
Cinik
b Department of Ophthalmology , Kocaeli University, Faculty of Medicine , Kocaeli , Turkey.
Nurşen
N
Yüksel
b Department of Ophthalmology , Kocaeli University, Faculty of Medicine , Kocaeli , Turkey.
Dilara
D
Pirhan
c Department of Ophthalmology , Arnavutkoy State Hospital , Istanbul , Turkey.
Mehmet Şehmuz
MŞ
Aslan
d Center for Regenerative Medicine and Stem Cell Research & Manufacturing (LivMedCell), Liv Hospital , Istanbul , Turkey.
Cansu
C
Subaşı
d Center for Regenerative Medicine and Stem Cell Research & Manufacturing (LivMedCell), Liv Hospital , Istanbul , Turkey.
Erdal
E
Karaöz
D000818:Animals; D002478:Cells, Cultured; D002921:Cicatrix / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D000068338:Everolimus / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects; D018463:Filtering Surgery / Q000009:adverse effects*; D005901:Glaucoma / Q000503:physiopathology / Q000601:surgery*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007429:Intraocular Pressure; D011817:Rabbits; D016896:Treatment Outcome; D014945:Wound Healing / Q000187:drug effects*
D007166:Immunosuppressive Agents; D000068338:Everolimus
Everolimus; glaucoma; mitomycin-C; trabeculectomy; wound-site healing