THE EFFECT OF TROSİNE KİNASE İNHİBİTOR NİNTEDANİB ON POST-TRAUMATİC PROLİFERATİVE VİTRORETİNOPATHY


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Müftüoğlu S. F.

NİCHE 2022 INTERNATİONAL CONGRESS OF HISTOLOGY AND EMBRYOLOGY, Antalya, Türkiye, 22 - 28 Mayıs 2022, ss.107-108

  • Yayın Türü: Bildiri / Özet Bildiri
  • Basıldığı Şehir: Antalya
  • Basıldığı Ülke: Türkiye
  • Sayfa Sayıları: ss.107-108
  • Hacettepe Üniversitesi Adresli: Evet

Özet

The effect of tyrosine kinase inhibitor nintedanib on post-traumatic
proliferative vitreoretinopathy

Introduction: Proliferative vitreoretinopathy (PVR) is most common cause of
rhegmatogenous retinal detachment surgery failure. It is a serious complication of
ocular trauma
 and characterized by contraction of membranes on
both sides in vitreous cavity close to retinal surface. Cytokines and growth factors are considered important molecules in pathogenesis of PVR. Nintedanib (BIBF1120) is the first tyrosine kinase inhibitor approved by FDA for treatment of Idiopathic Pulmonary Fibrosis. It is small molecule tyrosine kinase inhibitor that targets PDGF receptor-α and -β, FGF receptor-1–3, VEGF receptor-1–3. Nintedanib competitively binds to ATP-binding site of these receptors, thereby blocking intracellular signaling. It has been shown that intravitreal/oral Nintedanib reduces neovascularization, does not increase vaso-obliteration, and increases normal retinal vascularization.

Purpose: In our study, it was aimed to demonstrate that intravitreal nintedanib prevents
PVR formation on PVR model induced rabbit eyes by clinical and
histological examination.

Material-Method: 12 rabbits were divided into two groups; control and nintedanib. Eye of each rabbit was injured with 23G needle, causing puncture injury, and dispase solution was injected just above it. After induction of PVR model,PBS was injected into midvitreus of control group and 0.5% liposomal nintedanib was injected into midvitreus of nintenib group. They were examined weekly for four weeks, and, eyes were enucleated. Enucleated eyes were examined histologically with azan trichrome dye and marked with anti-collagen-1-antibody by immunofluorescence method then intensity measurement was performed.

Results: Posterior part of eyeball was noted that choriocapillary layer was much thinner in experimental group than control group. The difference between groups most probably  due to edema caused by the dilatation of veins in control group whereas the potential edema-reducing effect of nintedanib administeration in experimental group. Consistent with epiretinal membrane expected to be observed in disease model, fibrotic membrane formation extending towards the lens were also observed in front of retina and ciliary body of control group. However fibrotic membranes decreased in front of retina or were absent in the front of iris in nintedanib application group. (Figure 1). Terms of corrected-total-cell-fluorescence (CTCF) levels of subjects in control and those nintedanib treated groups are given in Table 1. According to mann-whitney-u test results applied, CTCF level of subjects administered nintedanib was found to be statistically significantly lower than control group. (p:0,004)

 

Conclusion: Nintedanib has been shown to reduce the occurrence of PVR without any significant side effects. So nintedanib may have potential property in treatment and prophylaxis of PVR.