Ocular neovascularization underlies major blinding eye diseases such as “wet” age‐related macular degeneration (AMD). Despite the successes of treatments targeting the vascular endothelial growth factor (VEGF) pathway, resistant and refractory patient populations necessitate discovery of new therapeutic targets. Using a forward chemical genetic approach, we identified the heme synthesis enzyme ferrochelatase (FECH) as necessary for angiogenesis in vitro and in vivo. FECH is overexpressed in wet AMD eyes and murine choroidal neovascularization; siRNA knockdown of Fech or partial loss of enzymatic function in the Fech
m1Pas mouse model reduces choroidal neovascularization. FECH depletion modulates endothelial nitric oxide synthase function and VEGF receptor 2 levels. FECH is inhibited by the oral antifungal drug griseofulvin, and this compound ameliorates choroidal neovascularization in mice when delivered intravitreally or orally. Thus, FECH inhibition could be used therapeutically to block ocular neovascularization.
Introduction:Cervical intraepithelial neoplasia and cervical cancer remain important health problems. Cervical cytology by Papanicolaou (Pap) smears is an effective means of screening for cervical premalignant and malignant conditions.Aim:The aim of this study was to assess the prevalence of cervical dysplasia in pre- and postmenopausal women in western Uttar Pradesh and to find out risk factors as far as possible.Materials and Methods:A total of 4,703 cases were enrolled, cervical scrape smears were collected and stained using Papanicolaou's method and hematoxylin and eosin stain. The emphasis was put on epithelial abnormalities and smears were classified according to The Bethesda System 2001.Results:81.06% (3812) smears were satisfactory according to The Bethesda System. Maximum numbers of cases (40.37%) were in age group 30-39 years. The epithelial abnormalities constituted 3.23% of all cases. Low-grade squamous intraepithelial lesion (LSIL) formed the largest number (1.36%), while high-grade squamous intraepithelial lesion (HSIL) formed 0.91%. Eleven cases of squamous cell carcinoma (SCC) were detected. The study has shown a relatively high prevalence of epithelial abnormalities in cervical smears with increasing age, parity, early age at first coitus (<20 year), and lower socioeconomic status in symptomatic women with clinical lesions on per speculum examination.Conclusion:Epithelial abnormalities of cervix are not uncommon in our setup and are associated with early age at marriage and parity.
Drs. Butler, Choi and Banerjee have no conflicts of interest or financial ties to disclose. Anna Martin and Kamna Gupta have no conflicts of interest or financial ties to disclose. Drs. Monfared and Stefanidis have research support from ExplORer Surgical however none of the research in the present report was funded by the above. Dr. Selzer is a consultant for Cook Biotech and PolyNovo, and has research support from Bard Mesh. However, none of the research in the present report was funded by the above.
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