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Letters to the Editor

Increased levels of vascular endothelial growth factor in aqueous humor of patients with diabetic retinopathy

Is it the whole truth?

Santhan Gopal, K S

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Indian Journal of Ophthalmology: Sep–Oct 2011 - Volume 59 - Issue 5 - p 405-406
doi: 10.4103/0301-4738.83629
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Dear Editor,

The article “Increased levels of vascular endothelial growth factor in the aqueous humor of patients with diabetic retinopathy” by Selim et al.

IJO ,Vol 58: 2010, was interesting. They have demonstrated elevated levels of vascular endothelial growth factor (VEGF) in aqueous humor of the diabetic patients with proliferative retinopathy and also a strong correlation between aqueous VEGF levels and severity of the condition.[1]

However, it is equally crucial to understand the role of other etiological factor/s in the pathogenesis of the disease. One such important factor is Insulin like growth factor 1 (IGF 1). Unfortunately, I did not find the mention of IGF 1 anywhere in the article, though the Insulin like growth factor 1 has been seriously implicated in the pathogenesis of diabetic retinopathy.

The articles about the increased intra ocular fluid levels of VEGF in diabetic retinopathy, first appeared in the literature in 1994[2] and the authors here have simply reconfirmed it in 2010. The conclusion of this study thus, merely reaffirms the results of many earlier studies carried out around 20 years ago, and a casual reader may inaccurately attribute a significant role to VEGF in diabetic retinopathy, ignoring the other important factors. Since the present study does not show any different or new result, that could further the management of diabetic retinopathy, role of IGF 1 in the etiopathogenesis of diabetic retinopathy should have received attention, if not more, at least in the discussion section.

It's pertinent to remember that IGF 1 is a key, direct regulator of VEGF levels and blood-retinal barrier breakdown in early stages of the disease[3] and that, VEGF itself is a slave mediator activated by hypoxia and by the interaction between IGF 1 and IGF 1 surface receptor (IGFR 1).

The IGF 1 interaction with IGFR 1 in the retinal pigment epithelial and retinal vascular endothelial cells, initiates an intra cellular cascade, leading to a number of reactions. One of the by, products of that cascade reaction is increased production and potentiation of VEGF. The VEGF merely plays a secondary role to IGF 1 in the initiation and progression of diabetic retinopathy. The former is even unable to sustain its angiogenic activity in the absence of IGF1.[3] Since the regression of diabetic retinopathy following intra vitreal anti-VEGF injection, is neither universal nor uniform, there has/have to be other etiological factor/s of diabetic retinopathy, besides VEGF. The critical role played by the IGF 1 in the initiation and progression of the diabetic retinopathy is well recognized and has been lucidly detailed in the article by Smith et al.[4] The intra ocular VEGF mirrors the elevated vitreous and retinal tissue levels of IGF 1. The elevation of IGF 1 precedes the onset of diabetic proliferative retinopathy, and a positive correlation has been observed between concentrations of IGF 1 in serum or vitreous fluid and extent of neovascularization in diabetic retinopathy.[5]

There are ongoing trials for modifying the IGF 1/IGFR 1 action to reverse or prevent the diabetic retinopathy.[6]

Strict metabolic control of the diabetes is essential to prevent the progression of retinopathy.

1. Selim KM, Sahan D, Muhittin T, Osman C, Mustafa O. Increased levels of vascular endothelial growth factor in the aqueous humor of patients with diabetic retinopathy Indian J Ophthalmol. 2010;58:375–9
2. Adamis AP, Miller JW, Bernal MT, D’Amico DJ, Folkman J, Yeo TK, et al Increased vascular endothelial growth factor levels in the vitreous of eyes with proliferative diabetic retinopathy Am J Ophthalmol. 1994;118:445–50
3. Poulaki V, Joussen AM, Mitsiades N, Mitsiades CS, Iliaki EF, Adamis AP. Insulin-like growth factor-I plays a pathogenetic role in diabetic retinopathy Am J Pathol. 2004;165:457–69
4. Smith LE, Shen W, Perruzzi C, Soker S, Kinose F, Xu X, et al Regulation of vascular endothelial growth factor-dependent retinal neovascularization by insulin-like growth factor-1 receptor Nat Med. 1999;5:1390–5
5. Chantelau E. Evidence that upregulation of serum IGF-1 concentration can trigger acceleration of diabetic retinopathy Br J Ophthalmol. 1998;82:725–7
6. Croxen R, Baarsma GS, Kuijpers RW, van Hagen PM. Somatostatin in diabetic retinopathy Pediatr Endocrinol Rev. 2004;1(Suppl 3):518–24
© 2011 Indian Journal of Ophthalmology | Published by Wolters Kluwer – Medknow