<p>Sir,</p> <p>I appreciate Dr. Khazaei′s interest in our article "Aqueous concentrations of VEGF and soluble VEGF receptor-1 (sVEGFR1) in diabetic retinopathy patients" and have read with interest the comments sent by him. <sup> <xref ref-type="bibr" rid="ref1">1</xref> </sup></p> <p>We found no significant difference in the aqueous fluid levels of vascular endothelial growth factor (VEGF) in nonproliferative diabetic retinopathy (NPDR) patients compared with nondiabetic patients, whereas that of sVEGFR-1 was significantly decreased in NPDR patients compared with nondiabetic patients. There was no significant different VEGF/sVEGFR-1 ratio between groups in our study (0.39 ± 0.04 in controls vs 0.29 ± 0.04 in NPDR patients, P = 0.3).</p> <p>We were aware of Dr. Waltenberger′s interesting explanation of angiogenic paradox based on the concept of VEGF resistance; <sup> <xref ref-type="bibr" rid="ref2">2</xref> </sup>however, it seems that not only VEGF resistance is not the case in microenvironment of the retina of diabetic patients, but also local increase in angiogenesis is associated with diabetic retinopathy.</p> <p>It has been shown that in early stages of NPDR, leakage of retinal microvessels is possibly caused by local VEGF production in areas of capillary nonperfusion, <sup> <xref ref-type="bibr" rid="ref3">3</xref> </sup>while VEGF messenger ribonucleic acid (mRNA) levels are increased in the ischemic retina of patients with advanced DR. <sup> <xref ref-type="bibr" rid="ref4">4</xref> </sup>With respect to imbalances between angiogenic and antiangiogenic factors, sVEGFR-1 has been suggested to act as a scavenger for VEGF-A, thereby protecting vessels from becoming leaky or proliferative. <sup> <xref ref-type="bibr" rid="ref5">5</xref> </sup>It has been suggested that production of sVEGFR-1 is also regulated by hypoxia and participates in regulation of angiogenesis. <sup> <xref ref-type="bibr" rid="ref6">6</xref> </sup>So, we speculate that decreased levels of sVEGFR-1, which increases the availability of VEGF-A may be an initial compensatory event in early steps of NPDR. However, further studies are needed to investigate other interesting possibilities which explain the role of VEGF and its receptors in DR.</p> </sec> </body> <back> <ref-list> <ref id="ref1"> <label>1</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>Javanmard</surname> <given-names>SH</given-names> </name> <name> <surname>Hassanpour</surname> <given-names>Z</given-names> </name> <name> <surname>Abbaspoor</surname> <given-names>Z</given-names> </name> <name> <surname>Naderian</surname> <given-names>GA</given-names> </name> <name> <surname>Jahanmard</surname> <given-names>M</given-names> </name> </person-group> <article-title>Aqueous concentrations of VEGF and soluble VEGF receptor-1 in diabetic retinopathy patients</article-title> <source>J Res Med Sci</source> <year>2012</year> <volume>17</volume> <fpage>1124</fpage> <lpage>7</lpage> </nlm-citation> </ref> <ref id="ref2"> <label>2</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>Waltenberger</surname> <given-names>J</given-names> </name> </person-group> <article-title>VEGF resistance as a molecular basis to explain the angiogenesis paradox in diabetes mellitus</article-title> <source>Biochem Soc Trans</source> <year>2009</year> <volume>37</volume> <fpage>1167</fpage> <lpage>70</lpage> </nlm-citation> </ref> <ref id="ref3"> <label>3</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>Mathews</surname> <given-names>MK</given-names> </name> <name> <surname>Merges</surname> <given-names>C</given-names> </name> <name> <surname>McLeod</surname> <given-names>DS</given-names> </name> <name> <surname>Lutty</surname> <given-names>GA</given-names> </name> </person-group> <article-title>Vascular endothelial growth factor and vascular permeability changes in human diabetic retinopathy</article-title> <source>Invest Ophthalmol Vis Sci</source> <year>1997</year> <volume>38</volume> <fpage>2729</fpage> <lpage>41</lpage> </nlm-citation> </ref> <ref id="ref4"> <label>4</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>Witmer</surname> <given-names>AN</given-names> </name> <name> <surname>Blaauwgeers</surname> <given-names>HG</given-names> </name> <name> <surname>Weich</surname> <given-names>HA</given-names> </name> <name> <surname>Alitalo</surname> <given-names>K</given-names> </name> <name> <surname>Vrensen</surname> <given-names>GF</given-names> </name> <name> <surname>Schlingemann</surname> <given-names>RO</given-names> </name> </person-group> <article-title>Altered expression patterns of VEGF receptors in human diabetic retina and in experimental VEGF-induced retinopathy in monkey</article-title> <source>Invest Ophthalmol Vis Sci</source> <year>2002</year> <volume>43</volume> <fpage>849</fpage> <lpage>57</lpage> </nlm-citation> </ref> <ref id="ref5"> <label>5</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>Shibuya</surname> <given-names>M</given-names> </name> </person-group> <article-title>Vascular endothelial growth factor receptor-1 (VEGFR-1/Flt-1): A dual regulator for angiogenesis</article-title> <source>Angiogenesis</source> <year>2006</year> <volume>9</volume> <fpage>225</fpage> <lpage>30</lpage> </nlm-citation> </ref> <ref id="ref6"> <label>6</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>Hornig</surname> <given-names>C</given-names> </name> <name> <surname>Barleon</surname> <given-names>B</given-names> </name> <name> <surname>Ahmad</surname> <given-names>S</given-names> </name> <name> <surname>Vuorela</surname> <given-names>P</given-names> </name> <name> <surname>Ahmed</surname> <given-names>A</given-names> </name> <name> <surname>Weich</surname> <given-names>HA</given-names> </name> </person-group> <article-title>Release and complex formation of soluble VEGFR-1 from endothelial cells and biological fluids</article-title> <source>Lab Invest</source> <year>2000</year> <volume>80</volume> <fpage>443</fpage> <lpage>54</lpage> </nlm-citation> </ref> <ref id="ref7"> <label>7</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"></person-group> <article-title></article-title> <source></source> <year></year> <volume></volume> <fpage></fpage> </nlm-citation> </ref> </ref-list> </back> </article>

JRMS

J Res Med Sci

Journal of Research in Medical Sciences

1735-1995 1735-7136

Medknow Publications Pvt Ltd

India

JRMS-18-825

24381630

Letter to Editor

Javanmard

Shaghayegh H

Physiology research center, Isfahan University of Medical Sciences, Isfahan, Iran

Address for correspondence:Shaghayegh Javanmard, Associate Professor of Physiology, Physiology research center, Isfahan University of Medical Sciences, Isfahan, Iran shaghayeghhaghjoo@yahoo.com

September 2013

18 9 825 825

2013

This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

<p>Sir,</p> <p>I appreciate Dr. Khazaei′s interest in our article "Aqueous concentrations of VEGF and soluble VEGF receptor-1 (sVEGFR1) in diabetic retinopathy patients" and have read with interest the comments sent by him. <sup> <xref ref-type="bibr" rid="ref1">1</xref> </sup></p> <p>We found no significant difference in the aqueous fluid levels of vascular endothelial growth factor (VEGF) in nonproliferative diabetic retinopathy (NPDR) patients compared with nondiabetic patients, whereas that of sVEGFR-1 was significantly decreased in NPDR patients compared with nondiabetic patients. There was no significant different VEGF/sVEGFR-1 ratio between groups in our study (0.39 ± 0.04 in controls vs 0.29 ± 0.04 in NPDR patients, P = 0.3).</p> <p>We were aware of Dr. Waltenberger′s interesting explanation of angiogenic paradox based on the concept of VEGF resistance; <sup> <xref ref-type="bibr" rid="ref2">2</xref> </sup>however, it seems that not only VEGF resistance is not the case in microenvironment of the retina of diabetic patients, but also local increase in angiogenesis is associated with diabetic retinopathy.</p> <p>It has been shown that in early stages of NPDR, leakage of retinal microvessels is possibly caused by local VEGF production in areas of capillary nonperfusion, <sup> <xref ref-type="bibr" rid="ref3">3</xref> </sup>while VEGF messenger ribonucleic acid (mRNA) levels are increased in the ischemic retina of patients with advanced DR. <sup> <xref ref-type="bibr" rid="ref4">4</xref> </sup>With respect to imbalances between angiogenic and antiangiogenic factors, sVEGFR-1 has been suggested to act as a scavenger for VEGF-A, thereby protecting vessels from becoming leaky or proliferative. <sup> <xref ref-type="bibr" rid="ref5">5</xref> </sup>It has been suggested that production of sVEGFR-1 is also regulated by hypoxia and participates in regulation of angiogenesis. <sup> <xref ref-type="bibr" rid="ref6">6</xref> </sup>So, we speculate that decreased levels of sVEGFR-1, which increases the availability of VEGF-A may be an initial compensatory event in early steps of NPDR. However, further studies are needed to investigate other interesting possibilities which explain the role of VEGF and its receptors in DR.</p> </sec> </body> <back> <ref-list> <ref id="ref1"> <label>1</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>Javanmard</surname> <given-names>SH</given-names> </name> <name> <surname>Hassanpour</surname> <given-names>Z</given-names> </name> <name> <surname>Abbaspoor</surname> <given-names>Z</given-names> </name> <name> <surname>Naderian</surname> <given-names>GA</given-names> </name> <name> <surname>Jahanmard</surname> <given-names>M</given-names> </name> </person-group> <article-title>Aqueous concentrations of VEGF and soluble VEGF receptor-1 in diabetic retinopathy patients</article-title> <source>J Res Med Sci</source> <year>2012</year> <volume>17</volume> <fpage>1124</fpage> <lpage>7</lpage> </nlm-citation> </ref> <ref id="ref2"> <label>2</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>Waltenberger</surname> <given-names>J</given-names> </name> </person-group> <article-title>VEGF resistance as a molecular basis to explain the angiogenesis paradox in diabetes mellitus</article-title> <source>Biochem Soc Trans</source> <year>2009</year> <volume>37</volume> <fpage>1167</fpage> <lpage>70</lpage> </nlm-citation> </ref> <ref id="ref3"> <label>3</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>Mathews</surname> <given-names>MK</given-names> </name> <name> <surname>Merges</surname> <given-names>C</given-names> </name> <name> <surname>McLeod</surname> <given-names>DS</given-names> </name> <name> <surname>Lutty</surname> <given-names>GA</given-names> </name> </person-group> <article-title>Vascular endothelial growth factor and vascular permeability changes in human diabetic retinopathy</article-title> <source>Invest Ophthalmol Vis Sci</source> <year>1997</year> <volume>38</volume> <fpage>2729</fpage> <lpage>41</lpage> </nlm-citation> </ref> <ref id="ref4"> <label>4</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>Witmer</surname> <given-names>AN</given-names> </name> <name> <surname>Blaauwgeers</surname> <given-names>HG</given-names> </name> <name> <surname>Weich</surname> <given-names>HA</given-names> </name> <name> <surname>Alitalo</surname> <given-names>K</given-names> </name> <name> <surname>Vrensen</surname> <given-names>GF</given-names> </name> <name> <surname>Schlingemann</surname> <given-names>RO</given-names> </name> </person-group> <article-title>Altered expression patterns of VEGF receptors in human diabetic retina and in experimental VEGF-induced retinopathy in monkey</article-title> <source>Invest Ophthalmol Vis Sci</source> <year>2002</year> <volume>43</volume> <fpage>849</fpage> <lpage>57</lpage> </nlm-citation> </ref> <ref id="ref5"> <label>5</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>Shibuya</surname> <given-names>M</given-names> </name> </person-group> <article-title>Vascular endothelial growth factor receptor-1 (VEGFR-1/Flt-1): A dual regulator for angiogenesis</article-title> <source>Angiogenesis</source> <year>2006</year> <volume>9</volume> <fpage>225</fpage> <lpage>30</lpage> </nlm-citation> </ref> <ref id="ref6"> <label>6</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"> <name> <surname>Hornig</surname> <given-names>C</given-names> </name> <name> <surname>Barleon</surname> <given-names>B</given-names> </name> <name> <surname>Ahmad</surname> <given-names>S</given-names> </name> <name> <surname>Vuorela</surname> <given-names>P</given-names> </name> <name> <surname>Ahmed</surname> <given-names>A</given-names> </name> <name> <surname>Weich</surname> <given-names>HA</given-names> </name> </person-group> <article-title>Release and complex formation of soluble VEGFR-1 from endothelial cells and biological fluids</article-title> <source>Lab Invest</source> <year>2000</year> <volume>80</volume> <fpage>443</fpage> <lpage>54</lpage> </nlm-citation> </ref> <ref id="ref7"> <label>7</label> <nlm-citation citation-type="journal"> <person-group person-group-type="author"></person-group> <article-title></article-title> <source></source> <year></year> <volume></volume> <fpage></fpage> </nlm-citation> </ref> </ref-list> </back> </article>