Lysyl oxidase activity in the ocular tissues and the role of LOX in proliferative diabetic retinopathy and rhegmatogenous retinal detachment.
OBJECTIVE
Lysyl oxidase (LOX) cross-links the side chain of collagen and elastin and thereby contributes to extracellular matrix (ECM) integrity. ECM remodeling is seen in various ocular diseases. Until now, there have been no reports on the LOX enzyme's activity in ocular tissues. The purpose of this study was to estimate LOX activity and expression in human donor ocular tissues and to measure the specific activity of LOX in the vitreous of proliferative diabetic retinopathy (PDR) and rhegmatogenous retinal detachment (RRD).


METHODS
Human donor eyeballs obtained from an eye bank were used to study tissue distribution of LOX. Human vitreous specimens were obtained during vitreoretinal surgery from PDR (n = 16) and RRD (n = 10). LOX activity was estimated by N-acetyl-3,7-dihydroxyphenoxazine assay, immunohistochemistry, and real-time polymerase chain reaction (RT-PCR). Matrix metalloprotease (MMP)-2 and -9 were quantified in the vitreous by sandwich enzyme-linked immunosorbent assay (ELISA).


RESULTS
The specific activity of LOX in ocular tissues was on the order of vitreous, iris ciliary body, lens, choroid RPE, and retina, which were comparable by mRNA expression and immunolocalization. The vitreous level of LOX activity decreased significantly in PDR and RRD, with an increase in total MMP-2 and -9 levels compared with normal donor vitreous.


CONCLUSIONS
LOX activity showed a statistically significant decrease in the vitreous of PDR and RRD relative to control specimens. This effect can contribute to the inadequate collagen cross-linking that causes the ECM changes that occur in these diseases.
Coral
Karunakaran
K
Biochemistry Research Department, Vision and Medical Research Foundation, Chennai, India.
Angayarkanni
Narayanasamy
N
Madhavan
Jagadeesan
J
Bharathselvi
Muthuvel
M
Ramakrishnan
Sivaramakrishnan
S
Nandi
Krishnendu
K
Rishi
Pukhraj
P
Kasinathan
Nachiappan
N
Krishnakumar
Subramanian
S
D000368:Aged; D002829:Choroid / Q000201:enzymology; D002924:Ciliary Body / Q000201:enzymology; D003930:Diabetic Retinopathy / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D007908:Lens, Crystalline / Q000201:enzymology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D016133:Polymerase Chain Reaction; D008249:Protein-Lysine 6-Oxidase / Q000096:biosynthesis / Q000235:genetics*; D012313:RNA / Q000235:genetics*; D012160:Retina / Q000201:enzymology; D012163:Retinal Detachment / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D018630:Vitreoretinopathy, Proliferative / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D014822:Vitreous Body / Q000201:enzymology
D012313:RNA; D008249:Protein-Lysine 6-Oxidase; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9