Deneysel olarak oluşturulan korneal neovaskülarizasyonlarda aflibersept, bevacizumab-doksisiklin ve sunitinib-hesperitin kombinasyonlarının etkinlikleri
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Tarih
2016
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Çanakkale Onsekiz Mart Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Amaç: Topikal aflibersept, sunitinib, bevacizumab-doksisiklin, sunitinib-doksisiklin ve sunitinib-hesperitin kombinasyonlarının korneal neovaskülarizasyon (KNV), apopitozis ve fibrozisi önleyici etkilerinin araştırılması amaçlandı. Gereç ve Yöntem: 48 ratın korneaları gümüş nitrat ile koterize edilerek KNV başlatıldı. Altı grup oluşturularak suni gözyaşı, aflibersept(20 mg/ml), sunitinib (0.5 mg/ml), sunitinib-hesperitin (0.5mg/ml-0.2 mg/ml), sunitinib-doksisiklin (0.5 mg/ml-20 mg/ml), bevacizumab-doksisiklin (5 mg/ml-20 mg/ml) tedavileri topikal olarak günde 2 kez uygulandı. 0, 3, 7 ve 15. günlerde korneal fotoğrafları çekildi. Korneal fotoğraflardaki vaskülarize alanın tüm korneal alana oranı bilgisayarda yüzde olarak hesaplandı. 15. günde rat gözleri enüklee edilip immunohistokimyasal boyamalar yapıldı.. Bulgular: KNV oranları 7.günde Sunitinib-Hesperitin (%1.1) ve Sunitinib (%4.8) gruplarında plaseboya (%33.9) göre daha düşüktü (p=0,02, p=0.029). 15. gündeki KNV oranları Sunitinib-Hesperitin (%20.8) grubunda, Plasebo (%74.6) ve Bevacizumab-Doksisiklin (%80.6) gruplarındaki göre anlamlı olarak düşüktü (p=0.04, p=0.023). Diğer gruplar arasında anlamlı fark yoktu. Tüm gruplarda plaseboya göre daha az CD31, VEGF, TUNEL ve ?-SMA pozitifliği bulundu. Kombinasyon gruplarında monoterapi gruplarına göre daha az VEGF, TUNEL ve ?-SMA pozitifliği saptandı. Sunitinib-Hesperitin ve Bevacizumab-Doksisiklin gruplarında diğer gruplara göre daha az VEGF pozitifliği bulunurken iki grup arasında istatistiksel olarak fark yoktu. TUNEL pozitifliği en az Sunitinib-Hesperitin ve Sunitinib-Doksisiklin gruplarında bulundu; ?-SMA pozitifliği açısından ise Sunitinib-Hesperitin ve Bevacizumab-Doksisiklin gruplarında en düşük oran saptandı. Sonuç: Sunitinib ve Sunitinib-Hesperitin gruplarında diğer gruplara göre vi daha az vaskülarizasyon saptandı. Sunitinibin Hesperitin ile birlikte kullanımı monoterapiye göre daha az apopitozis ve fibrozise yol açmaktadır.
Aim: The aim was to research the preventive effects of topical aflibercept, sunitinib, bevacizumab-doxycycline, sunitinib-doxycycline and sunitinib-hesperitin combinations on corneal neovascularization (CNV), apoptosis and fibrosis. Material and Method: The corneas of 48 rats were cauterized with silver nitrate to initiate CNV. Six groups were treated with topical treatments applied 2 times a day: artificial tears, aflibercept (20 mg/ml), sunitinib (0.5 mg/ml), sunitinib-hesperitin (0.5 mg/ml-0.2 mg/ml), sunitinib-doxycycline (0.5 mg/ml-20 mg/ml) and bevacizumab-doxycycline (5 mg/ml-20 mg/ml). Cornea photographs were taken on days 0, 3, 7 and 15. The vascularized area on corneal photographs was calculated as a percentage of the whole area with a computer. On the 15th day rats' eyes were enucleated and immunohistochemical staining performed. Results: On the 7th day the CNV rates in the sunitinib-hesperitin (1..1%) and sunitinib (4.8%) groups were lower compared to placebo (33.9%) (p=0.02, p=0.029). On the 15th day, the CNV rates in the sunitinib-hesperitin (20.8%) group were significantly lower compared to the placebo (74.6%) and bevacizumab-doxycycline (80.6%) groups (p=0.04, p=0.023). There was no significant difference with the other groups. All groups had lower CD31, VEGF, TUNEL and ?-SMA positivity compared to placebo. In combination groups, there was lower VEGF, TUNEL and ?-SMA positivity identified compared to monotherapy groups. While the sunitinib-hesperitin and bevacizumab-doxycycline groups had lower VEGF positivity compared to other groups, there was no statistical difference between the two groups. TUNEL positivity was lowest in the sunitinib-hesperitin and sunitinib-doxycycline groups, while the lowest values for ?-SMA positivity were identified in the sunitinib-hesperitin and bevacizumab-doxycycline groups. viii Conclusion: Less vascularization was observed in the sunitinib and sunitinib-hesperitin groups compared to the other groups. The use of sunitinib with hesperitin caused less apoptosis and fibrosis compared to monotherapy.
Aim: The aim was to research the preventive effects of topical aflibercept, sunitinib, bevacizumab-doxycycline, sunitinib-doxycycline and sunitinib-hesperitin combinations on corneal neovascularization (CNV), apoptosis and fibrosis. Material and Method: The corneas of 48 rats were cauterized with silver nitrate to initiate CNV. Six groups were treated with topical treatments applied 2 times a day: artificial tears, aflibercept (20 mg/ml), sunitinib (0.5 mg/ml), sunitinib-hesperitin (0.5 mg/ml-0.2 mg/ml), sunitinib-doxycycline (0.5 mg/ml-20 mg/ml) and bevacizumab-doxycycline (5 mg/ml-20 mg/ml). Cornea photographs were taken on days 0, 3, 7 and 15. The vascularized area on corneal photographs was calculated as a percentage of the whole area with a computer. On the 15th day rats' eyes were enucleated and immunohistochemical staining performed. Results: On the 7th day the CNV rates in the sunitinib-hesperitin (1..1%) and sunitinib (4.8%) groups were lower compared to placebo (33.9%) (p=0.02, p=0.029). On the 15th day, the CNV rates in the sunitinib-hesperitin (20.8%) group were significantly lower compared to the placebo (74.6%) and bevacizumab-doxycycline (80.6%) groups (p=0.04, p=0.023). There was no significant difference with the other groups. All groups had lower CD31, VEGF, TUNEL and ?-SMA positivity compared to placebo. In combination groups, there was lower VEGF, TUNEL and ?-SMA positivity identified compared to monotherapy groups. While the sunitinib-hesperitin and bevacizumab-doxycycline groups had lower VEGF positivity compared to other groups, there was no statistical difference between the two groups. TUNEL positivity was lowest in the sunitinib-hesperitin and sunitinib-doxycycline groups, while the lowest values for ?-SMA positivity were identified in the sunitinib-hesperitin and bevacizumab-doxycycline groups. viii Conclusion: Less vascularization was observed in the sunitinib and sunitinib-hesperitin groups compared to the other groups. The use of sunitinib with hesperitin caused less apoptosis and fibrosis compared to monotherapy.
Açıklama
Tıp Fakültesi, Göz Hastalıkları Ana Bilim Dalı
Anahtar Kelimeler
Göz Hastalıkları, Eye Diseases
