|Year : 2000 | Volume
| Issue : 4 | Page : 307-9
Raised platelet thiobarbituric acid-reacting substances in proliferative Eales' disease.
P Srivastava, S Saxena, VK Khanna, D Kumar, R Nath, PK Seth
King George's Medical College, Lucknow, India
King George's Medical College, Lucknow
Source of Support: None, Conflict of Interest: None
BACKGROUND: Platelets are an elective site for oxidative stress owing to their high content of polyunsaturated fatty acid. Increased lipid peroxidation and elevated platelet thiobarbituric acid-reacting substances (TBARS) signal oxidative stress. This possibly leads to retinal neovascularization in Eales' disease. METHODS: TBARS levels were estimated in consecutive cases of Eales' disease with neovascularisation (n = 26), Eales' disease without neovascularisation (n = 17) and healthy controls (n = 17). RESULTS: Platelet TBARS levels in the cases of Eales' disease with neovascularisation, Eales' disease without neovascularisation, and healthy controls were 0.66 +/- 0.1, 0.57 +/- 0.11 and 0.42 +/- 0.14 n moles TBARS formed/hour/10(8) platelets respectively. Student's t-test showed a significant increase in platelet TBARS levels in cases with neovascularisation as compared to cases without neovascularization (p < 0.05) and healthy controls (p < 0.01). CONCLUSION: The increase in platelet TBARS levels in proliferative Eales' disease is consistent with an emerging view that lipid peroxides may be associated with retinal neovascularisation.
Keywords: Adolescent, Adult, Biological Markers, blood, Blood Platelets, metabolism, Comparative Study, Disease Progression, Humans, Lipid Peroxidation, ph
|How to cite this article:|
Srivastava P, Saxena S, Khanna V K, Kumar D, Nath R, Seth P K. Raised platelet thiobarbituric acid-reacting substances in proliferative Eales' disease. Indian J Ophthalmol 2000;48:307
|How to cite this URL:|
Srivastava P, Saxena S, Khanna V K, Kumar D, Nath R, Seth P K. Raised platelet thiobarbituric acid-reacting substances in proliferative Eales' disease. Indian J Ophthalmol [serial online] 2000 [cited 2021 May 8];48:307. Available from: https://www.ijo.in/text.asp?2000/48/4/307/14838
Eales' disease is an idiopathic obliterative vasculopathy that primarily affects the peripheral retina in young adults.1 Retinal changes include perivasculitis, peripheral nonperfusion and neovascularisation.[2-4] Visual loss is characteristically caused by recurrent vitreous haemorrhages and their sequelae.
Ocular angiogenesis is a complex pathophysiologic process. Several factors have been isolated that play a key role in the regulation of angiogenesis. The involvement of peptide growth factors namely, insulin-like growth factor and transforming growth factors alpha and beta has been documented in several vascular retinopathies. The influence of stimulating growth factors is counterbalanced by a number of antiproliferative agents. The net results of these oposing factors in the vascular endothelial cells determine the outcome of angiogenic haemostasis. Many angiogenesis-dependent diseases including those of ocular neovascularisation may be driven by stimuli including cytokine growth factors, inflammation, hypoxia and angiogenic mediators including nitric oxide.
Retinal hypoxia is known to stimulate neovascularisation in ischaemic proliferative retinopathies. The retina because of its high content of polyunsaturated fatty acids (PUFA), is prone to oxidative stress. Platelets also contain a high proportion of PUFA, which serve as potent substrate for oxidants. The role of oxidative stress in causation of diabetic vascular complications is well documented.[10-14] Elevated thiobarbituric acid-reacting substances (TBARS) have been reported in erythrocytes and vitreous of cases of Eales' disease. [15,16] Our recent studies [17, on platelets in Eales' disease cases have shown an enhanced oxidative stress as evident by increased lipid peroxidation and decreased activity of superoxide dismutase, catalase and reduced glutathione. A tertiary-care centre-based case control study was undertaken to study the association of lipid peroxidation and retinal neovascularisation in Eales' disease.
| Materials and Methods|| |
Forty-three consecutive cases of Eales' disease presenting at the retina clinic of King George's Medical College, Lucknow and 17 healthy controls were included. All were males. Participants gave their informed consent prior to inclusion in the study. Diabetes mellitus, sickle cell haemoglobinopathy, blood dyscrasias, sarcoidosis and collagen vascular disorders were ruled out after appropriate history and laboratory investigations. All patients underwent detailed ophthalmological examination including Snellen's visual acuity, slitlamp biomlcroscopy, indirect ophthalmoscopy and fluorescein angiography. Patients with previous laser photocoagulation and /or vitrectomy were excluded from this study.
Blood samples were collected from both cases and controls. The first group consisted of cases of Eales' disease with neovascularisation (n=26). The second group consisted of cases of Eales' disease without neovascularisation (n=17). The third group consisted of healthy controls (n=17).
Blood (15 ml) was drawn by venipuncture using a plastic disposable syringe and a 20-gauge needle. Trisodium citrate (3.89%) was used as an anticoagulant. TBARS level in platelets was estimated by the method of Boehme et al.19 The data were statistically analyzed by the student's t-test and the statistical significance was set at p<0.05. Results are presented as means ± S.D.
| Results|| |
This study included 43 patients with Eales' disease, and 17 healthy controls. The mean age of the first group of patients (Eales' disease with neovascularisation) was 24.6±5.7 years (range 18-34 years). The mean age of second group patients (Eales' disease without neovascularisation) was 24.5±4.8 years (range 18-32 years). The mean age of healthy controls was 24.9+5.4 years (18-31 years). Platelet TBARS levels in the cases of Eales' disease with neovascularisation, Eales' disease without neovascularisation and healthy controls were 0.66 ± 0.1, 0.57 ± 0.11 and 0.42 ± 0.14 n moles TBARS formed/hour/108 platelets respectively. A significant increase in platelet TBARS levels was observed in cases with neovascularisation as compared to the cases without neovascularisation (p < 0.05) and healthy controls (p< 0.01).
| Discussion|| |
Occurrence of retinal ischaemia and neovascularisation is well established in Eales' disease. [20,21] It is now recognised that the normal vascular state reflects an exquisitely complex balance of endogenous positive and negative mediators of angiogenesis, a concept referred to as the angiogenesis model of haemostasis. Loss of this balance in favour of neovascularisation predominates in many pathologic conditions including Eales' disease.
The concept of angiogenic haemostasis in the eye and the consequences of its disruption have increasing operational value in understanding the mechanisms underlying ocular angiogenesis. Substantial data now implicate vascular endothelial growth factor (VEGF) as a dominant factor in proliferative retinopathies. An angiogenic stimulus such as VEGF induced by hypoxic conditions, directs vascular endothelial cell orientation, migration, proliferation and adhesion. Lumen formation and blood flow through these new channels complete this process, which is regarded as a type of vasculogenesis because new vessels develop from precursor cells. Despite the growing recognition of VEGF in angiogenesis-dependent diseases, emerging data suggest that multiple growth factors and other influences may be involved in pathologic angiogenesis.
Multiple cytokine signals govern the proliferative response of vascular endothelial cells in angiogenesis. Mechanical influences on the vascular endothelial cell cytoskeleton and nucleus modulate the influence of angiogenic cytokines. Reactive free radical, such as nitric oxide and other vasostimulatory molecules can produce this effect, possibly promoting angiogenesis through vasodilation.
Armstrong et al have proposed a mechanism in diabetic retinopathy, whereby the lipid peroxides induce the synthesis of cytokines particularly tumour necrosis factor alpha. These in turn could lead to an increase in transforming growth factors alpha and beta which are associated with neovascularisation in the retina.
Elevated TBARS levels have been reported in the subretinal fluid of cases of proliferative diabetic retinopathy affected by retinal detachment as compared to nondiabetic patients. A variety of processes might increase the production of reactive oxygen species at the retinal level. One is the oxidative stress caused by conditions of transient hypoxia-hyperoxia. [25,26] The oxidative alterations of retinal tissue in diabetic patients may also be attributed to the chronic defficiency of antioxidants in reduced form as a consequence of monosaccharaide auto-oxidation, NADPH oxidation and formation of protein glycation products. [27,28]
Our recent study has shown that retinal antigens (retinal S-antigen and Interphotoreceptor Retinoid Binding Protein) may play a role in the aetiopathogenesis of Eales' disease. An extraneous agent could result in exposure of normally sequestered uveitopathogenic antigens of the immune system leading to an immune response in the eye that may initiate the disease process. Retinal S-antigen and Interphotoreceptor Retinoid Binding Protein have been shown to induce production of reactive free radicals such as nitric oxide and superoxide., 
Enhanced oxidative stress has been reported in cases of Eales' disease. [15, In the present study, a significant increase in platelet TBARS levels was observed in cases of Eales' disease with retinal neovascularisation as compared to cases without neovascularisation. The increase in platelet TBARS levels is consistent with an emerging view that antioxidant defences decline in association with the disease process and lipid peroxides may be associated with retinal neovascularisation.
| References|| |
Gieser SC, Murphy RP. In: Ryan SJ, editor. Retina
. Vol. 2. Medical Retina
. St. Louis:C V Mosby Co. 1994. pp 1503-8.
Atmaca L S, Idil A, Gunduz K. Visualization of retinal vasculitis in Eales' disease. Ocular Immunol Inflammol
Saxena S, Kumar D. Visual outcome of branch retinal vein occlusion in Eales' disease. Ann Ophthalmol
Saxena S, Kumar D. Macular involvement in Eales' disease. Ann Ophthalmol
Kumar D, Saxena R C, Saxena S. Vitreous haemorrhage in Eales' disease. Afro-Asian J Ophthalmol
Casey R, Li WW. Factors controlling ocular angiogenesis Am J Ophthalmol
Schultz AS, Grant MB. Neovascular growth factors. Eye
Stefannsson E. Oxygen and diabetic eye disease. Graefes Arch Clin Exp Ophthalmol
Srivastava S, Joshi CS, Sethi PPS, Agrawal AK, Srivastava SK, Seth PK. Altered platelet function in non-insulin dependent diabetes mellitus (NIDDM). Thrombosis
Guigliano D, Paolisso G, Ceriello A. Oxidative stress and diabetic complications. Diabetes Care
Wolff SP. The potential role of oxidative stress in diabetes and its complications: Novel implications for theory and therapy. In:Crabbe MJC, editor. Diabetic Complications: Scientific and Clinical Aspects
. London:Churchill Livingston; 1987:167-21.
Jennings PE, McLaren M, Scott NA, Saniabadi JF. The relationship of oxidative stress to thrombotic tendency in type I diabetic patients with diabetic retinopathy. Diabetic Med
Caimi G, Ventimiglia G, Presti RL, Romano A, Montana M, Catania A, et al. Membrane fluidity. Membrane lipid pattern and cytosolic Ca2+
content in platelets from a group of type II diabetic patients with macrovascular complications. Diabetes Care
Rema M, Mohan V, Bhaskar A, Shanmugasundaram KR. Does oxidant stress play a role in diabetic retinopathy. Indian J Ophthalmol
Bhooma V, Sulochana KN, Biswas J, Ramakrishnan S. Eales' disease: Accumulation of reactive oxygen intermediates and lipid peroxides and decrease of antioxidants causing inflammation, neovascularization and retinal damage. Curr Eye
Sulochna KN, Biswas J, Ramakrishnan S. Eales' disease: Increased oxidation and peroxidation products of membrane constituents chiefly lipids and decreased antioxidant enzymes and reduced glutathione in vitreous. Curr Eye
Res 1999; 18:254-59.
Saxena S, Khanna VK, Kumar D, Srivastava P, Seth PK. Enhanced oxidative stress in Eales' disease. Ann Ophthalmol
. (In press).
Saxena S, Kumar D, Srivastava P, Khanna VK, Seth PK. Low levels of platelet glutathione in Eales disease. Med Sci
Boehme DH, Kosecki R, Carson S, Stern F, Marks N. Lipoperoxidation in human and rat brain tissue: Developmental and regional studies. Brain
Atmaca L S, Idil A, Gunduz K. Visualization of retinal vasculitis in Eales' disease. Ocular Immunol Inflammol
Das T, Biswas J, Kumar A, Nagpal P N, Namperumalsamy P, Patnaik B, et al. Eales' disease. Indian J Ophthalmol
Asahara T, Murohara T, Sullivan A, Silver M, Van Der Zee R, Li T, et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science
Armstrong D, Hartnett M, Browne R, Ueda T, Jenis E, Al Jada A, et al. Lipid-peroxide induced synthesis of cytokine growth factors during neovascularization in the retina. Invest Ophthalmol Vis Sci
Grattagliano I, Vendemiale G, Boscia F, Micelli-Ferrari T, Cardia L, Altomare E. Oxidative retinal products and ocular damages in diabetic patients.Free Rad Biol Med
Jamieson D, Chance B, Cadenas E, Boveris A. The relationship of free radical production in hyperoxia. Annu Rev Physiol
Williamson JR, Chang K, Frangos M, Hasan KS, Ido Y, Kawamura T, et al. Hyperglycemia pseudohypoxia and diabetic complications. Diabetes
Hunt JV, Dean RT, Wolff SP. Hydroxyl radical production and autooxidative glycosylation:Glucose autoxidation as the cause of protein damage in experimental glycation model of diabetes mellitus and ageing. Biochem J
Ahmed MU, Thorpe R, Bayness JW. Identification of N-carboxymethyllysine as a degradation product of fructoselysine in glycated protein. J Biol Chem
Saxena S, Rajasingh J, Biswas S, Kumar D, Shinohara T, Singh V K. Cellular immune response to retinal S-antigen and interphotoreceptor retinoid binding protein fragments in Eales' disease. Pathobiology
Wu GS, Zhang J, Rao NA. Peroxynitrite and oxidative damage in experimental autoimmune uveitis. Invest Ophthalmol Vis Sci
Shimizu K, Zhang J, Riono WP, Wu GS, Rao NA. Retinal S-antigen and IRBP induce nitric oxide production in macrophages. Invest Ophthalmol Vis Sci
Support: Council of Science and Technology (U.P.) and Council of Scientific and Industrial Research, New Delhi, India.
|This article has been cited by|
||Ealesę disease: Oxidant stress and weak antioxidant defence
| ||Ramakrishnan, S., Rajesh, M., Sulochana, K. |
| ||Indian Journal of Ophthalmology. 2007; 55(2): 95-102 |
||Increase in Fe3+/Fe2+ ratio and iron-induced oxidative stress in Eales disease and presence of ferrous iron in circulating transferrin
| ||Selvi, R., Angayarkanni, N., Bharathselvi, M., Sivaramakrishna, R., Anisha, T., Jyotirmoy, B., Vasanthi, B. |
| ||Current Eye Research. 2007; 32(7-8): 677-683 |
||Decreased platelet membrane fluidity in retinal periphlebitis in Ealesę disease
| ||Saxena, S., Srivastava, P., Kumar, D., Khanna, V.K., Seth, P.K. |
| ||Ocular Immunology and Inflammation. 2006; 14(2): 113-116 |
||Response time and safety profile of pulsed oral methotrexate therapy in idiopathic retinal periphlebitis
| ||Bali, T., Saxena, S., Kumar, D., Nath, R. |
| ||European Journal of Ophthalmology. 2005; 15(3): 374-378 |
||Determination of carbonyl group content in plasma proteins as a useful marker to assess impairment in antioxidant defense in patients with Ealesę disease
| ||Rajesh, M., Sulochana, K.N., Coral, K., Punitham, R., Biswas, J., Babu, K., Ramakrishnan, S. |
| ||Indian Journal of Ophthalmology. 2004; 52(2): 139-144 |
||A new staging system for idiopathic retinal periphlebitis
| ||Saxena, S., Kumar, D. |
| ||European Journal of Ophthalmology. 2004; 14(3): 236-239 |
||Accumulation of 8-hydroxydeoxyguanosine and its relationship with antioxidant parameters in patients with Ealesę disease: Implications for antioxidant therapy
| ||Rajesh, M., Ramesh, A., Ravi, P.E., Balakrishnamurthy, P., Coral, K., Punitham, R., Sulochana, K.N., (...), Ramakrishnan, S. |
| ||Current Eye Research. 2003; 27(2): 103-110 |