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Irreversible loss of eyesight caused by glaucoma was estimated to
be the second main reason for blindness worldwide. Progression
of the disease is due to changes around the optic nerve and others.
One type of glaucoma called Primary Congenital Glaucoma
(PCG) which has knowledge gap. We aim to study a mutation
called (c.182G>A, p.Gly61Glu) within CYP1B1 gene which was
reported in PCG. We report the CYP1B1 mutation in the context
of microglia, astrocytes and mesenchymal stem cells. The cellular
behaviour of those cells needed to maintain eye homeostasis was
investigated in response to CYP1B1 mutation. CRISPR technology
was used to edit normal CYP1B1 genes within normal astrocytes,
microglia and stem cells in vitro. Metabolic activities dropped by
40% after 72 hrs of mutation insertion. In addition, NADP/NADPH
reducing equivalent process decreased by 50% on average after 72
hrs of manipulation. The cytokines measured on mutated microglia
and astrocytes showed progressive activation leading to apoptosis
or abnormality as compared to the control. The results suggested a
progressive inflammation that was induced by mutant (p.Gly61Glu)
on CYP1B1. Furthermore, the mutant enhances microglia�s loss of
activity. We are the first to show the direct impact of the mutation
on microglia. This progressive inflammation might be responsible
for primary congenital glaucoma complications which could be
avoided by an anti-inflammatory regimen. Moreover, microglia is
important for ganglion cells survival along with clearing pathogens
and inflammation. The loss of their activities may jeopardize the
homeostasis around optic nerve environment and complicate
protection to optic nerve components (such as retinal ganglion
cells and glial cells).
Biography
Bahauddeen M. Alrfaei is working in King Abdullah International Medical Research Centre (KAIMRC), Cellular Therapy Dept. Stem Cells and Regenerative Medicine Unit. He has published more than 35 papers in reputed journals and has been serving as an editorial board member of repute. His research interest are Cancer Stem Cells, Regenerative Medicine, Pathology, miRNA, Cancer Biology, Flow Cytometer, Cell Signalling, Gene Expression, Primary Cell Culture, Epigenetics, Molecular Biology, Cancer Research, Genetics and Cell Culture.
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