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Biochemistry of the eye

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 7

cataract
crystalin

UV filter

Glutathione (GSH)

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Crystalin protein of the lens

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3D structure of crystalin protein

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Amino acid sequence of crystalin protein

>gi|10518338|ref|NP_066269.1| crystallin, gamma C [Homo sapiens]

MGKITFYEDRAFQGRSYETTTDCPNLQPYFSRCNSIRVESGCWML
YERPNYQGQQYLLRRGEYPDYQQWM GLSDSIRSCCLIPQTVSHR
LRLYEREDHKGLMMELSEDCPSIQDRFHLSEIRSLHVLEGCWVLYE
LPNYR GRQYLLRPQEYRRCQDWGAMDAKAGSLRRVVDLY

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Crystalin gene locus

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 Crystalin mRNA

>gi|13377000|ref|NM_020989.2| Homo sapiens crystallin, gamma C (CRYGC), mRNA

GGGCCCCTTTTGTGTTGTTCTTGCCAACGCAGCAGCCATCCTGCTATATAGACTGG
CTGTGCAGCCGCAG GCCCCATCACACTGAACTCGCATCATCCGTGTCAACCCAGC
CATGGGGAAGATCACCTTCTATGAGGACA GGGCCTTCCAGGGCCGCAGCTACGA
AACCACCACTGACTGCCCCAACCTGCAGCCGTATTTCAGCCGCTG CAACTCCATC
CGGGTGGAGAGCGGCTGCTGGATGCTCTATGAGCGTCCCAACTACCAAGGTCAAC
AATAC TTGCTGCGGCGAGGGGAGTACCCCGACTACCAGCAATGGATGGGCCTCAG
CGACTCCATCCGCTCCTGTT GTCTCATCCCCCAAACAGTCTCCCACAGGCTGCGGC
TGTACGAGAGGGAAGACCACAAAGGCCTCATGAT GGAGCTGAGTGAAGACTGCCC
CAGCATCCAGGACCGCTTCCACCTCAGCGAGATCCGTTCCCTCCACGTG CTGGAG
GGCTGCTGGGTCCTCTACGAGCTCCCCAACTACCGGGGGCGGCAATACCTGCTGA
GGCCCCAAG AGTACAGGCGGTGCCAGGACTGGGGGGCCATGGATGCTAAGGCAG
GCTCTTTGCGGAGAGTGGTGGATTT GTATTAAAATAGCTTAACACTACCAATTTCCC
ATTTTGGAACCTAATAAATATTTAGTCTGCATTGCTGG C

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Crystalin aggregation causes cataract formation

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UV FILTER
Protects crystalin from uv radiation

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Glutathione
(GSH) UV

Oxidation

GSH
Free radical

Damage of uv filter and crystalin protein

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Cell metabolism
or UV

toxic

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glutathione structure

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DIABETIC LENS
HYPERGLICEMIA

POLYOL PATHWAY ACTIVATION

SORBITOL ACCUMULATION

OSMOTIC LENS

LENS SWELLING AND CATARACT

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DIABETIC LENS

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DIABETIC RETINOPATY

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 DIABETIK RETINOPATHY

ANGIOPATHY

HYPOXIA

ANGIOGENIC FACTOR MATRIX PROTEASE

NEOVASCULARIZATION 26
NEOVASKULARIZATION

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ANGIOGENIC FACTOR VEGF

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VEGF PROTEIN

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AMINO ACID SEQUENCE VEGF PROTEIN

>gi|56204719|emb|CAI19965.1| vascular endothelial growth

factor [Homo sapiens]

MNFLLSWVHWSLALLLYLHHAKWSQAAPMAEGGGQNHHE
VVKFMDVYQRSYCHPIETLVDIFQEYPDEIEYIFKPSCVPLMR
CGGCCNDEGLECVPTEESNITMQIMRIKPHQGQHIGEMSFL
QHNKCECRPKKDRARQENPCGPCSERRKHLFVQDPQTCK
CSCKNTDSRCKARQLELNERTCRSLTRKD

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VEGF gene locus

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MATRIX PROTEASE PROTEIN

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MATRIX PROTEASE
PROTEIN

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LOCUS MATRIX PROTEASE GENE

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RETINOBLASTOMA

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RETINOBLASTOMA PROTEIN

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AMINO ACID SEQUENCE OF RETINOBLASTOMA PROTEIN

>gi|4506435|ref|NP_000312.1| retinoblastoma 1 [Homo sapiens]

MPPKTPRKTAATAAAAAAEPPAPPPPPPPEEDPEQDSGPEDLPLVRLEFEETEEPDFTALCQKLKIPDHV
RERAWLTWEKVSSVDGVLGGYIQKKKELWGICIFIARVDLDEMSFTLLSYRKTYEISVHKFFNLLKEIDT
STKVDNAMSRLLKKYDVLFALFSKLERTCELIYLTQPSSSISTEINSALVLKVSWITFLLAKGEVLQMED
DLVISFQLMLCVLDYFIKLSPPMLLKEPYKTAVIPINGSPRTPRRGQNRSARIAKQLENDTRIIEVLCKE
HECNIDEVKNVYFKNFIPFMNSLGLVTSNGLPEVENLSKRYEEIYLKNKDLDRRLFLDHDKTLQTDSIDS
FETQRTPRKSNLDEEVNIIPPHTPVRTVMNTIQQLMMILNSASDQPSENLISYFNNCTVNPKESILKRVK
DIGYIFKEKFAKAVGQGCVEIGSQRYKLGVRLYYRVMESMLKSEEERLSIQNFSKLLNDNIFHMSLLACA
LEVVMATYSRSTSQNLDSGTDLSFPWILNVLNLKAFDFYKVIESFIKAEGNLTREMIKHLERCEHRIMES
LAWLSDSPLFDLIKQSKDREGPTDHLESACPLNLPLQNNHTAADMYLSPVRSPKKKGSTTRVNSTANAET
QATSAFQTQKPLKSTSLSLFYKKVYRLAYLRLNTLCERLLSEHPELEHIIWTLFQHTLQNEYELMRDRHL
DQIMMCSMYGICKVKNIDLKFKIIVTAYKDLPHAVQETFKRVLIKEEEYDSIIVFYNSVFMQRLKTNILQ
YASTRPPTLSPIPHIPRSPYKFPSSPLRIPGGNIYISPLKSPYKISEGLPTPTKMTPRSRILVSIGESFG
TSEKFQKINQMVCNSDRVLKRSAEGSNPPKPLKKLRFDIEGSDEADGSKHLPGESKFQQKLAEMTSTRTR
MQKQKMNDSMDTSNKEEK

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RETINOBLASTOMA GENE LOCUS

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 mRNA OF RETINOBLASTOMA

>gi|4506434|ref|NM_000321.1| Homo sapiens retinoblastoma 1 (including osteosarcoma) (RB1), mRNA

TTCCGGTTTTTCTCAGGGGACGTTGAAATTATTTTTGTAACGGGAGTCGGGAGAGGACGGGGCGTGCCCC GCGTGCGCGCGCGTCGTCCTCCCCGGCGCTCCTCCACAGCTCGCTGGCTCCCGCCG
GCCGCCCAAAACCCCCCGAAAAACGGCCGCCACCGCCGCCGCTGCCGCCGCGGAACCCCCGGCACCGCCG CCGCCGCCCCCTCCTGAGGAGGACCCAGAGCAGGACAGCGGCCCGGAGGACCT
AGTTTGAAGAAACAGAAGAACCTGATTTTACTGCATTATGTCAGAAATTAAAGATACCAGATCATGTCAG AGAGAGAGCTTGGTTAACTTGGGAGAAAGTTTCATCTGTGGATGGAGTATTGGGAGGTT
AAAAAGGAACTGTGGGGAATCTGTATCTTTATTGCACGAGTTGACCTAGATGAGATGTCGTTCACTTTAC TGAGCTACAGAAAAACATACGAAATCAGTGTCCATAAATTCTTTAACTTACTAAAAGAAAT
TACCAAAGTTGATAATGCTATGTCAAGACTGTTGAAGAAGTATGATGTATTGTTTGCACTCTTCAGCAAA TTGGAAAGGACATGTGAACTTATATATTTGACACAACCCAGCAGTTCGATATCTACTGAAA
CATTGGTGCTAAAAGTTTCTTGGATCACATTTTTATTAGCTAAAGGGGAAGTATTACAAATGGAAGATGA TCTGGTGATTTCATTTCAGTTAATGCTATGTGTCCTTGACTATTTTATTAAACTCTCACCTC
CTCAAAGAACCATATAAAACAGCTGTTATACCCATTAATGGTTCACCTCGAACACCCAGGCGAGGTCAGA ACAGGAGTGCACGGATAGCAAAACAACTAGAAAATGATACAAGAATTATTGAAGTTCTC
TGAATGTAATATAGATGAGGTGAAAAATGTTTATTTCAAAAATTTTATACCTTTTATGAATTCTCTTGGA CTTGTAACATCTAATGGACTTCCAGAGGTTGAAAATCTTTCTAAACGATACGAAGAAATTTAT
ATAAAGATCTAGATCGAAGATTATTTTTGGATCATGATAAAACTCTTCAGACTGATTCTATAGACAGTTT TGAAACACAGAGAACACCACGAAAAAGTAACCTTGATGAAGAGGTGAATATAATTCCTCCA
GTTAGGACTGTTATGAACACTATCCAACAATTAATGATGATTTTAAATTCTGCAAGTGATCAACCTTCAG AAAATCTGATTTCCTATTTTAACAACTGCACAGTGAATCCAAAAGAAAGTATACTGAAAAGA
TATAGGATACATCTTTAAAGAGAAATTTGCTAAAGCTGTGGGACAGGGTTGTGTCGAAATTGGATCACAG CGATACAAACTTGGAGTTCGCTTGTATTACCGAGTAATGGAATCCATGCTTAAATCAGAA
TATCCATTCAAAATTTTAGCAAACTTCTGAATGACAACATTTTTCATATGTCTTTATTGGCGTGCGCTCT TGAGGTTGTAATGGCCACATATAGCAGAAGTACATCTCAGAATCTTGATTCTGGAACAGAT
CCATGGATTCTGAATGTGCTTAATTTAAAAGCCTTTGATTTTTACAAAGTGATCGAAAGTTTTATCAAAG CAGAAGGCAACTTGACAAGAGAAATGATAAAACATTTAGAACGATGTGAACATCGAATCAT
TGCATGGCTCTCAGATTCACCTTTATTTGATCTTATTAAACAATCAAAGGACCGAGAAGGACCAACTGAT CACCTTGAATCTGCTTGTCCTCTTAATCTTCCTCTCCAGAATAATCACACTGCAGCAGATA
CTCCTGTAAGATCTCCAAAGAAAAAAGGTTCAACTACGCGTGTAAATTCTACTGCAAATGCAGAGACACA AGCAACCTCAGCCTTCCAGACCCAGAAGCCATTGAAATCTACCTCTCTTTCACTGTTTTA
TATCGGCTAGCCTATCTCCGGCTAAATACACTTTGTGAACGCCTTCTGTCTGAGCACCCAGAATTAGAAC ATATCATCTGGACCCTTTTCCAGCACACCCTGCAGAATGAGTATGAACTCATGAGAGAC
CCAAATTATGATGTGTTCCATGTATGGCATATGCAAAGTGAAGAATATAGACCTTAAATTCAAAATCATT GTAACAGCATACAAGGATCTTCCTCATGCTGTTCAGGAGACATTCAAACGTGTTTTGATCA
AGTATGATTCTATTATAGTATTCTATAACTCGGTCTTCATGCAGAGACTGAAAACAAATATTTTGCAGTA TGCTTCCACCAGGCCCCCTACCTTGTCACCAATACCTCACATTCCTCGAAGCCCTTACAAG
TCACCCTTACGGATTCCTGGAGGGAACATCTATATTTCACCCCTGAAGAGTCCATATAAAATTTCAGAAG GTCTGCCAACACCAACAAAAATGACTCCAAGATCAAGAATCTTAGTATCAATTGGTGAAT
TTCTGAGAAGTTCCAGAAAATAAATCAGATGGTATGTAACAGCGACCGTGTGCTCAAAAGAAGTGCTGAA GGAAGCAACCCTCCTAAACCACTGAAAAAACTACGCTTTGATATTGAAGGATCAGATGA
GTAAACATCTCCCAGGAGAGTCCAAATTTCAGCAGAAACTGGCAGAAATGACTTCTACTCGAACACGAAT GCAAAAGCAGAAAATGAATGATAGCATGGATACCTCAAACAAGGAAGAGAAATGAGGA
GGTGGACACTGTGTACACCTCTGGATTCATTGTCTCTCACAGATGTGACTGTATAACTTTCCCAGGTTCT GTTTATGGCCACATTTAATATCTTCAGCTCTTTTTGTGGATATAAAATGTGCAGATGCAAT
GAGTCCTAAGCCACTTGAAATGTTAGTCATTGTTATTTATACAAGATTGAAAATCTTGTGTAAATCCTGC CATTTAAAAAGTTGTAGCAGATTGTTTCCTCTTCCAAAGTAAAATTGCTGTGCTTTATGGAT
TGGCCCTAGAGTGGGAGTCCTGATAACCCAGGCCTGTCTGACTACTTTGCCTTCTTTTGTAGCATATAGG TGATGTTTGCTCTTGTTTTTATTAATTTATATGTATATTTTTTTAATTTAACATGAACACCC
TGTGTCCTATCTATCTTCCAAATGCAATTTGATTGACTGCCCATTCACCAAAATTATCCTGAACTCTTCT GCAAAAATGGATATTATTAGAAATTAGAAAAAAATTACTAATTTTACACATTAGATTTTATTTT
GGAATCTGATATACTGTGTGCTTGTTTTATAAAATTTTGCTTTTAATTAAATAAAAGCTGGAAGCAAAGT ATAACCATATGATACTATCATACTACTGAAACAGATTTCATACCTCAGAATGTAAAAGAACT
ATTTTCTTCATCCAACTTATGTTTTTAAATGAGGATTATTGATAGTACTCTTGGTTTTTATACCATTCAG ATCACTGAATTTATAAAGTACCCATCTAGTACTTGAAAAAGTAAAGTGTTCTGCCAGATCTTA
AGGACCCTAACACAGTATATCCCAAGTGCACTTTCTAATGTTTCTGGGTCCTGAAGAATTAAGATACAAA TTAATTTTACTCCATAAACAGACTGTTAATTATAGGAGCCTTAATTTTTTTTTCATAGAGAT
TTGCATCTCAAAATTATTCTGCCCTCCTTAATTTGGGAAGGTTTGTGTTTTCTCTGGAATGGTACATGTC TTCCATGTATCTTTTGAACTGGCAATTGTCTATTTATCTTTTATTTTTTTAAGTCAGTATGGT
TGGCATGTTCAAAGCCACATTATTTCTAGTCCAAAATTACAAGTAATCAAGGGTCATTATGGGTTAGGCA TTAATGTTTCTATCTGATTTTGTGCAAAAGCTTCAAATTAAAACAGCTGCATTAGAAAAAG
TCCCCTCCCCTACACCTAAAGGTGTATTTAAACTATCTTGTGTGATTAACTTATTTAGAGATGCTGTAAC TTAAAATAGGGGATATTTAAGGTAGCTTCAGCTAGCTTTTAGGAAAATCACTTTGTCTAACT
TTTTTAAAAAGAAATCTGGTCTTGTTAGAAAACAAAATTTTATTTTGTGCTCATTTAAGTTTCAAACTTA CTATTTTGACAGTTATTTTGATAACAATGACACTAGAAAACTTGACTCCATTTCATCATTGTTT
GAATATCATACAAATCAGTTAGTTTTTAGGTCAAGGGCTTACTATTTCTGGGTCTTTTGCTACTAAGTTC ACATTAGAATTAGTGCCAGAATTTTAGGAACTTCAGAGATCGTGTATTGAGATTTCTTAAAT
AGATATTATTGCTTTATTGCTTTTTTGTATTGGTTAAAACTGTACATTTAAAATTGCTATGTTACTATTT TCTACAATTAATAGTTTGTCTATTTTAAAATAAATTAGTTGTTAAGAGTC

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RETINOBLASTOMA PROTEIN FUNGCTION

CELL
PROLIFERATION

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 CELL
PROLIFERATION

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RETINOBLASTOMA gene mutation

Over activation ofE2F

Cell proliferation

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RETINITIS PIGMENTOSA

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ROD AND CONE

<>

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STRUCTURE OF THE RETINA

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RHODOPSIN PROTEIN

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PHOTOTRANSDUCTION

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PHOTOTRANSDUCTION

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RODOPSIN PROTEIN

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AMINO ACID SEQUENCE OF RODOPSIN PROTEIN

>gi|4506527|ref|NP_000530.1| rhodopsin [Homo sapiens]

MNGTEGPNFYVPFSNATGVVRSPFEYPQYYLAEPWQFS
MLAAYMFLLIVLGFPINFLTLYVTVQHKKLRTPLNYILLNLA
VADLFMVLGGFTSTLYTSLHGYFVFGPTGCNLEGFFATLG
GEIALWSLVVLAIERYVVVCKPMSNFRFGENHAIMGVAFT
WVMALACAAPPLAGWSRYIPEGLQCSCGIDYYTLKPEVN
NESFVIYMFVVHFTIPMIIIFFCYGQLVFTVKEAAAQQQES
ATTQKAEKEVTRMVIIMVIAFLICWVPYASVAFYIFTHQGS
NFGPIFMTIPAFFAKSAAIYNPVIYIMMNKQFRNCMLTTICC
GKNPLGDDEASATVSKTETSQVAPA

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mRNA OF RHODOPSIN
>gi|7262389|ref|NM_000539.2| Homo sapiens rhodopsin (opsin 2, rod pigment) (retinitis pigmentosa 4, autosomal dominant) (RHO), mRNA
AGAGTCATCCAGCTGGAGCCCTGAGTGGCTGAGCTCAGGCCTTCGCAGCATTCTTGGGTGGGAGCAGCCA
CGGGTCAGCCACAAGGGCCACAGCCATGAATGGCACAGAAGGCCCTAACTTCTACGTGCCCTTCTCCAAT
GCGACGGGTGTGGTACGCAGCCCCTTCGAGTACCCACAGTACTACCTGGCTGAGCCATGGCAGTTCTCCA
TGCTGGCCGCCTACATGTTTCTGCTGATCGTGCTGGGCTTCCCCATCAACTTCCTCACGCTCTACGTCAC
CGTCCAGCACAAGAAGCTGCGCACGCCTCTCAACTACATCCTGCTCAACCTAGCCGTGGCTGACCTCTTC
ATGGTCCTAGGTGGCTTCACCAGCACCCTCTACACCTCTCTGCATGGATACTTCGTCTTCGGGCCCACAG
GATGCAATTTGGAGGGCTTCTTTGCCACCCTGGGCGGTGAAATTGCCCTGTGGTCCTTGGTGGTCCTGGC
CATCGAGCGGTACGTGGTGGTGTGTAAGCCCATGAGCAACTTCCGCTTCGGGGAGAACCATGCCATCATG
GGCGTTGCCTTCACCTGGGTCATGGCGCTGGCCTGCGCCGCACCCCCACTCGCCGGCTGGTCCAGGTACA
TCCCCGAGGGCCTGCAGTGCTCGTGTGGAATCGACTACTACACGCTCAAGCCGGAGGTCAACAACGAGTC
TTTTGTCATCTACATGTTCGTGGTCCACTTCACCATCCCCATGATTATCATCTTTTTCTGCTATGGGCAG
CTCGTCTTCACCGTCAAGGAGGCCGCTGCCCAGCAGCAGGAGTCAGCCACCACACAGAAGGCAGAGAAGG
AGGTCACCCGCATGGTCATCATCATGGTCATCGCTTTCCTGATCTGCTGGGTGCCCTACGCCAGCGTGGC
ATTCTACATCTTCACCCACCAGGGCTCCAACTTCGGTCCCATCTTCATGACCATCCCAGCGTTCTTTGCC
AAGAGCGCCGCCATCTACAACCCTGTCATCTATATCATGATGAACAAGCAGTTCCGGAACTGCATGCTCA
CCACCATCTGCTGCGGCAAGAACCCACTGGGTGACGATGAGGCCTCTGCTACCGTGTCCAAGACGGAGAC
GAGCCAGGTGGCCCCGGCCTAAGACCTGCCTAGGACTCTGTGGCCGACTATAGGCGTCTCCCATCCCCTA
CACCTTCCCCCAGCCACAGCCATCCCACCAGGAGCAGCGCCTGTGCAGAATGAACGAAGTCACATAGGCT
CCTTAATTTTTTTTTTTTTTTTAAGAAATAATTAATGAGGCTCCTCACTCACCTGGGACAGCCTGAGAAG
GGACATCCACCAAGACCTACTGATCTGGAGTCCCACGTTCCCCAAGGCCAGCGGGATGTGTGCCCCTCCT
CCTCCCAACTCATCTTTCAGGAACACGAGGATTCTTGCTTTCTGGAAAAGTGTCCCAGCTTAGGGATAAG
TGTCTAGCACAGAATGGGGCACACAGTAGGTGCTTAATAAATGCTGGATGGATGCAGGAAGGAATGGAGG
AATGAATGGGAAGGGAGAACATATCTATCCTCTCAGACCCTCGCAGCAGCAGCAACTCATACTTGGCTAA
TGATATGGAGCAGTTGTTTTTCCCTCCCTGGGCCTCACTTTCTTCTCCTATAAAATGGAAATCCCAGATC
CCTGGTCCTGCCGACACGCAGCTACTGAGAAGACCAAAAGAGGTGTGTGTGTGTCTATGTGTGTGTTTCA
GCACTTTGTAAATAGCAAGAAGCTGTACAGATTCTAGTTAATGTTGTGAATAACATCAATTAATGTAACT
AGTTAATTACTATGATTATCACCTCCTGATAGTGAACATTTTGAGATTGGGCATTCAGATGATGGGGTTT
CACCCAACCTTGGGGCAGGTTTTTAAAAATTAGCTAGGCATCAAGGCCAGACCAGGGCTGGGGGTTGGGC
TGTAGGCAGGGACAGTCACAGGAATGCAGGATGCAGTCATCAGACCTGAAAAAACAACACTGGGGGAGGG
GGACGGTGAAGGCCAAGTTCCCAATGAGGGTGAGATTGGGCCTGGGGTCTCACCCCTAGTGTGGGGCCCC
AGGTCCCGTGCCTCCCCTTCCCAATGTGGCCTATGGAGAGACAGGCCTTTCTCTCAGCCTCTGGAAGCCA
CCTGCTCTTTTGCTCTAGCACCTGGGTCCCAGCATCTAGAGCATGGAGCCTCTAGAAGCCATGCTCACCC
GCCCACATTTAATTAACAGCTGAGTCCCTGATGTCATCCTTACTCGAAGAGCTTAGAAACAAAGAGTGGG
AAATTCCACTGGGCCTACCTTCCTTGGGGATGTTCATGGGCCCCAGTTTCCAGTTTCCCTTGCCAGACAA
GCCCATCTTCAGCAGTTGCTAGTCCATTCTCCATTCTGGAGAATCTGCTCCAAAAAGCTGGCCACATCTC
TGAGGTGTCAGAATTAAGCTGCCTCAGTAACTGCTCCCCCTTCTCCATATAAGCAAAGCCAGAAGCTCTA
GCTTTACCCAGCTCTGCCTGGAGACTAAGGCAAATTGGGCCATTAAAAGCTCAGCTCCTATGTTGGTATT
AACGGTGGTGGGTTTTGTTGCTTTCACACTCTATCCACAGGATAGATTGAAACTGCCAGCTTCCACCTGA
TCCCTGACCCTGGGATGGCTGGATTGAGCAATGAGCAGAGCCAAGCAGCACAGAGTCCCCTGGGGCTAGA 55
GGTGGAGGAGGCAGTCCTGGGAATGGGAAAAACCCCA
GENE LOCUS OF RHODOPSIN

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RHODOPSIN GENE MUTATION

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CORNEA ULCER

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OCULAR SURFACE

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LYSOZYME

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how lysozyme degrade bacteria cell wall

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CORNEAL ULCER

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 BACTERIA Activation of leukocyte and keratocyte

PROTEASE KOLAGENASE PROTEASE

(katepsin, elastase)

STROMAL CORNEAL DEGRADATION

ULCER
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PROTEASE

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Thank you

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