الفهرس 
OCULAR GENETICSPRINCIBLES OF MOLECULAROnly 14 pages are availabe for public view
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Abstract
DNA ( or deoxyribo nucleic acid) is the molecule that carries the genetic information in all cellular forms of life composed of long chain of nucleotide
Each nucleotide consists of three components:
- A nitrogenous base: cytosine (C), guanine (G), adenine (A) or thymine (T) .
- A five-carbon sugar molecule (deoxyribose in the case of DNA) .
- A phosphate molecule.
DNA is packaged into the nucleus to be protected against damage from external factors to be used for direct protein synthesis and produce the structure of the cell in process called gene expression which involves two main stages , transcription (the production of messenger RNA ) and Translation ( the use of mRNA to direct protein synthesis) . .
During this process of gene expression or just after the expression some alteration in DNA or the product leading to appearance of the mutations which can occur in a variety of forms in eye diseases , including missense, nonsense , or RNA-splicing mutation .
To identify and control of such mutation we have to recognize DNA , there are several methods for DNA recognition like Electrophoretic mobility-shift assay , Binding-site selection assay , Fluorescence In Situ Hybridization , PCR and gene cloning .
Ocular hereditary disorders can be transmitted according to various modes of genetic transmission, including autosomal dominant, autosomal recessive, X-linked dominant (rare) or recessive, multifactorial inheritance, and cytoplasmic inheritance.
from these disorders there are a number of ocular diseases and conditions which could be suitable for treatment with ocular gene therapy. These diseases fall into two categories, ocular disease caused by a specific genetic disorder, whether dominant or recessive , and diseases which have no currently known genetic basis but instead could be treated with the introduction of genes expressing proteins useful in the treatment of the condition.
This gene therapy done through introduction of genetic material in vivo or ex vivo into the cells of an affected organism in order to: exchange a defective gene, manipulate a disease-related gene or introduce an additional gene copy for over expression of the encoded protein to generate a curative biological effect.
Both non viral or viral vectors can be used as vector systems for gene transfer.
Non viral vectors like naked DNA , oligonucleotides and lipoplexes and polyplexes , examples for viral gene delivery method is using viral vectors like Retrovirus , Lentiviruses, Adenovirus and Herbes Simplex virus.
The most recent approaches of gene therapy like using Ribosomes , SMaRTtm , stem cells , nanotechnology and antisense therapy now are well established to serve this new type of management.
Eye is ideal target organ for gene therapy of both inherited and acquired disorders for example in ocular neovascularization using of vascular endothelial growth factor, pigmented epithelium derived Factor (PEDF) , endostatin, angiostatin and angiopoietins show inhibition of retinal and choroidal neovascularization.
In glaucoma, intraocular delivery of neuroprotective molecules it can rescue retinal ganglion cells after optic nerve injury. Experimental gene based therapies targeting the trabecular meshwork by metalloproteinase 1 affect on steroid induced glaucoma.
In retinoblastoma , Mallikarjuna and his colleagues studied differential protein profile of RB tumors , The analysis revealed two of proteins upregulated are alpha crystallin A (CRYAA) and peroxiredoxin 6 (PRDX6) which can inhibit apoptotic processes in tumor cells.
In retinitis pigmentosa (RP) , there are two methods to correct the abnormal genes these two methods are gene augmentation therapies, where a normal gene is inserted into the genome to replace nonviable or diseased genes using a carrier vector and gene silencing therapies, in which the expression of the mutated gene is inhibited by use of ribosome or RNA interference .
In Briard dog model of LCA resulting from mutations in RPE65, gene therapy utilizing AAV-mediated RPE65 was shown to restore visual function, an effect that has been documented to last for more than five years.
In AMD, a relatively small number of genes with large effect have been identified, several of which alter the alternative complement pathway.
Allotopic Expression is one of the most promising emerging technologies in gene therapy of LHON where in a nuclear version of the mitochondrial gene is constructed by partially recoding the mtDNA gene in the nuclear genetic code.
Adeno-associated viral vectors are being successfully applied to the cornea, that shows promising trial of gene therapy in corneal dystrophies .
Many trials now using PAX 6 gene suggest potential therapeutic applications for PAX6 in inherited ocular diseases caused by this gene like Peter`s anomaly and aniridia.
Finally , these disorders I have mentioned just examples of application of gene therapy in ocular diseases, and many other trials of gene therapy are waiting to come out in the real clinical life .