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Th e n e w e n g l a n d j o u r n a l o f me dicine
n engl j med 367;2 nejm.org july 12, 2012184
Diabetic Retinopathy
To the Editor: In their review article on diabetic
retinopathy (March 29 issue),1 Antonetti et al. de-
scribe the retinal dysfunction associated with
diabetes as a change in the retinal neurovascu-
lar unit, alluding to energy homeostasis, but donot refer to the
article by Arden.2 In this article,
Arden points out that the 120 million rods have
the highest metabolic rate of any cell, requiring a
great deal of energy and oxygen, especially in the
dark.3 Since the rods are avascular, the partial
pressure of oxygen among the mitochondria is
essentially zero. Thus, in dark adaptation, the
retina uses so much oxygen that it is nearly
pathologically anoxic and at risk if the oxygen
supply is reduced. Arden reports on patients with
absent rod function (i.e., with retinitis pigmen-
tosa) and coexisting diabetes. In contrast to an
expected rate of diabetic retinopathy of 40% in
such patients, the condition did not develop in any
of these cases.
This finding may provide the link to obstruc-
tive sleep apnea. The hypoxic load that obstruc-
tive sleep apnea delivers has been linked to the
development of diabetic retinopathy, and inter-
vention with continuous positive airway pressure
has been shown to be beneficial.4,5
Panagis Drakatos, M.D.
Christopher Kosky, M.B.Adrian J. Williams, M.B.
Guys and St. Thomas NHS Foundation TrustLondon, United
[email protected]
No potential conflict of interest relevant to this letter was
re-
ported.
1. Antonetti DA, Klein R, Gardner TW. Diabetic retinopathy.
N Engl J Med 2012;366:1227-39.2. Arden GB. The absence of
diabetic retinopathy in patients
with retinitis pigmentosa: implications for pathophysiology
andpossible treatment. Br J Ophthalmol 2001;85:366-70.3. Hagins WA,
Ross PD, Tate RL, Yoshikami S. Transduction
heats in retinal rods: tests of the role of cGMP by
pyroelectriccalorimetry. Proc Natl Acad Sci U S A 1989;86:1224-8.4.
Wong A, Merritt S, Butt AN, Williams A, Swaminathan R.Effect of
hypoxia on circulating levels of retina-specific messen-
ger RNA in type 2 diabetes mellitus. Ann N Y Acad Sci 2008;
1137:243-52.5. Mason RH, Klire CA, Groves DC, et al. Visual
improvement
following continuous positive airway pressure therapy in
dia-betic subjects with clinically significant macular oedema
and
obstructive sleep apnoea: proof of principle study.
Respiration2011 December 20 (Epub ahead of print).
To the Editor: Antonetti et al. describe emerg-
ing therapeutic targets beyond vascular endothe-
lial growth factor (VEGF) signaling in patients with
diabetic retinopathy, such as the platelet-derived
growth factor (PDGF) pathway. Although the au-thors emphasize
the salutary role of PDGF as a pro-
survival cytokine to maintain pericyte viability
and normal vascularization in transgenic mouse
models of diabetic retinopathy, studies in humans
have suggested the opposite effect. In fact, several
studies have shown elevated PDGF concentrations
in vitreous samples from patients with diabetic
retinopathy.1,2 Like VEGF, PDGF is a proangiogen-
ic growth factor that may promote aberrant neo-
vascularization in diabetic retinopathy.3 Further-
more, PDGF may stimulate the formation and
traction of epiretinal membranes in patients with
diabetic retinopathy, leading to tractional retinal
detachment.4 Indeed, the development of inhibi-
tors that antagonize PDGF signaling in patho-
logic retinal neovascularization a hallmark of
proliferative diabetic retinopathy remains an
active area of ophthalmic drug development.5
Rajesh C. Rao, M.D.Washington University School of MedicineSt.
Louis, [email protected]
Brian J. Dlouhy, M.D.University of Iowa Hospitals and
ClinicsIowa City, IA
No potential conflict of interest relevant to this letter was
re-ported.
1. Praidou A, Papakonstantinou E, Androudi S, Georgiadis
N,Karakiulakis G, Dimitrakos S. Vitreous and serum levels of
vas-
cular endothelial growth factor and platelet-derived growth
fac-
tor and their correlation in patients with non-proliferative
dia-betic retinopathy and clinically signif icant macula oedema.
Acta
Ophthalmol 2011;89:248-54.2. Praidou A, Klangas I,
Papakonstantinou E, et al. Vitreous
and serum levels of platelet-derived growth factor and their
cor-relation in patients with proliferative diabetic retinopathy.
Curr
Eye Res 2009;34:152-61.
3. Vinores SA, Seo MS, Okamoto N, et al. Experimental modelsof
growth factor-mediated angiogenesis and blood-retinal bar-
rier breakdown. Gen Pharmacol 2000;35:233-9.4. Mori K, Gehlbach
P, Ando A, et al. Retina-specific expres-
sion of PDGF-B versus PDGF-A: vascular versus nonvascular
pro-
liferative retinopathy. Invest Ophthalmol Vis Sci
2002;43:2001-6.5. Jo N, Mailhos C, Ju M, et al. Inhibition of
platelet-derived
growth factor B signaling enhances the eff icacy of
anti-vascularendothelial growth factor therapy in multiple models
of ocular
neovascularizat ion. Am J Pathol 2006;168:2036-53.
DOI: 10.1056/NEJMc1205011
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