Suofu Qin

Roy S. Chuck

PPARs in Eye Biology and Disease

The angiogenic, neovascular proliferative 
retinopathies, proliferative diabetic retinopathy (PDR), and 
age-dependent macular degeneration (AMD) complicated by choroidal 
neovascularization (CNV),  also termed exudative or 
&#x201C;wet&#x201D; AMD, are common causes of blindness. The 
antidiabetic thiazolidinediones (TZDs), rosiglitazone, and 
troglitazone are PPAR<svg style="vertical-align:-2.34499pt;width:8.0625px;" id="M2" height="9.9375" version="1.1" viewBox="0 0 8.0625 9.9375" width="8.0625"  xmlns="http://www.w3.org/2000/svg">
	<g transform="matrix(1.25,0,0,-1.25,0,9.9375)">
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				<tspan style="font-size: 12.50px; " x="0" y="0">𝛾</tspan>
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</svg> agonists with demonstrable antiproliferative, and 
anti-inflammatory effects, in vivo, were shown to ameliorate PDR 
and CNV in rodent models, implying the potential efficacy of TZDs 
for treating proliferative retinopathies in humans. Activation of 
the angiotensin II type 1 receptor (AT1-R) propagates 
proinflammatory and proliferative pathogenic determinants 
underlying PDR and CNV. The antihypertensive dual AT1-R blocker 
(ARB), telmisartan, recently was shown to activate PPAR<svg style="vertical-align:-2.34499pt;width:8.0625px;" id="M3" height="9.9375" version="1.1" viewBox="0 0 8.0625 9.9375" width="8.0625"  xmlns="http://www.w3.org/2000/svg">
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				<tspan style="font-size: 12.50px; " x="0" y="0">𝛾</tspan>
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		</g>
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</svg> and improve glucose and 
lipid metabolism and to  clinically  improve PDR and CNV in rodent 
models. Therefore, the TZDs and telmisartan, clinically approved 
antidiabetic and antihypertensive drugs, respectively, may be 
efficacious for treating and attenuating PDR and CNV humans. 
Clinical trials are needed to test these 
possibilities.

Harrihar A. Pershadsingh

David M. Moore

PPAR<svg style="vertical-align:-3.56265pt" height="12.175" version="1.1" viewBox="0 0 8.6374998 12.175" width="8.6374998" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg"><g transform="matrix(.017,-0,0,-.017,.062,7.675)"><path id="x1D6FE" d="M478 372q0 -39 -31 -97t-61 -98t-78 -98q-45 -55 -73 -102q-13 -79 -13 -197q-11 -11 -43.5 -25.5t-53.5 -15.5l-15 17q5 35 26 101.5t47 123.5q8 72 -1.5 174.5t-37.5 178.5q-14 37 -29 37q-20 0 -67 -65l-25 21q37 60 73 90.5t63 30.5q47 0 72 -112q13 -56 17.5 -141.5&#xA;t0.5 -143.5h2q155 193 155 297q0 26 -12 47q-5 8 -5 15q0 16 12.5 27t29.5 11q21 0 34 -21t13 -55z" /></g></svg> Agonists: Potential as Therapeutics for Neovascular Retinopathies

The peroxisome proliferator-activated receptors (PPAR's) are members of the steroid/thyroid nuclear receptor, superfamily of transcription factors. There are currently three known PPAR subtypes, <svg style="vertical-align:-0.1254pt;width:8.9375px;" id="M2" height="7.1750002" version="1.1" viewBox="0 0 8.9375 7.1750002" width="8.9375"  xmlns="http://www.w3.org/2000/svg">
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				<tspan style="font-size: 12.50px; " x="0" y="0">𝛼</tspan>
			</text>

		</g>
	</g>
</svg>, <svg style="vertical-align:-2.29482pt;width:8.8500004px;" id="M3" height="13.425" version="1.1" viewBox="0 0 8.8500004 13.425" width="8.8500004"  xmlns="http://www.w3.org/2000/svg">
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				<tspan style="font-size: 12.50px; " x="0" y="0">𝛽</tspan>
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</svg>, and <svg style="vertical-align:-2.34499pt;width:8.0625px;" id="M4" height="9.9375" version="1.1" viewBox="0 0 8.0625 9.9375" width="8.0625"  xmlns="http://www.w3.org/2000/svg">
	<g transform="matrix(1.25,0,0,-1.25,0,9.9375)">
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			<text transform="matrix(1,0,0,-1,-71.95,66.44)">
				<tspan style="font-size: 12.50px; " x="0" y="0">𝛾</tspan>
			</text>

		</g>
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</svg>. The PPARs are now recognized participants in a number 
of biological pathways some of which are implicated in the 
pathogenesis of age-related macular degeneration (AMD). These 
include immune modulation, lipid regulation, and 
oxidant/antioxidant pathways important to the onset and 
progression of &#x201c;dry&#x201d; AMD, and vascular endothelial 
growth factor (VEGF) mediated pathways that stimulate choroidal 
neovascularization (CNV), characteristic of &#x201c;wet&#x201d; AMD.  
PPAR-<svg style="vertical-align:-0.1254pt;width:8.9375px;" id="M5" height="7.1750002" version="1.1" viewBox="0 0 8.9375 7.1750002" width="8.9375"  xmlns="http://www.w3.org/2000/svg">
	<g transform="matrix(1.25,0,0,-1.25,0,7.175)">
		<g transform="translate(72,-66.26)">
			<text transform="matrix(1,0,0,-1,-71.95,66.44)">
				<tspan style="font-size: 12.50px; " x="0" y="0">𝛼</tspan>
			</text>

		</g>
	</g>
</svg> is found in retina and also on vascular cells 
important to formation of CNV.  At this time, however, relatively 
little is known about potential contributions of PPAR-<svg style="vertical-align:-0.1254pt;width:8.9375px;" id="M6" height="7.1750002" version="1.1" viewBox="0 0 8.9375 7.1750002" width="8.9375"  xmlns="http://www.w3.org/2000/svg">
	<g transform="matrix(1.25,0,0,-1.25,0,7.175)">
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				<tspan style="font-size: 12.50px; " x="0" y="0">𝛼</tspan>
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</svg> to the pathogenesis of dry and wet AMD. This review examines current literature for potential roles of PPAR-<svg style="vertical-align:-0.1254pt;width:8.9375px;" id="M7" height="7.1750002" version="1.1" viewBox="0 0 8.9375 7.1750002" width="8.9375"  xmlns="http://www.w3.org/2000/svg">
	<g transform="matrix(1.25,0,0,-1.25,0,7.175)">
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				<tspan style="font-size: 12.50px; " x="0" y="0">𝛼</tspan>
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</svg> in the pathogenesis and potential treatment of AMD with emphasis on prevention and treatment of wet AMD.

Marisol del V Cano

Peter L. Gehlbach

PPAR-<svg style="vertical-align:-0.1638pt" height="8.1625004" version="1.1" viewBox="0 0 10.7375 8.1625004" width="10.7375" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg"><g transform="matrix(.017,-0,0,-.017,.062,7.9)"><path id="x1D736" d="M505 450h125l-163 -259q-1 -4 -1 -12q0 -19 1 -23q9 -98 41 -98q36 0 58 76l24 -7q-34 -139 -121 -139q-32 0 -57.5 24t-31.5 55q-72 -77 -181 -77q-73 0 -114 44t-41 124q0 118 79 210q79 93 197 93q51 0 86 -27t50 -71zM369 281q0 141 -62 141q-43 0 -95 -84&#xA;q-52 -82 -52 -195q0 -50 15 -83t42 -33q35 0 79 57q43 58 67 121q6 35 6 76z" /></g></svg> Ligands as Potential Therapeutic Agents for Wet Age-Related Macular Degeneration

Cellular oxidative stress plays an important role in retinal pigment epithelial (RPE) cell death during aging and the development of age-related macular degeneration.  Early reports indicate that during phagocytosis of rod outer segments, there is an increase of RPE oxidative stress and an upregulation of PPAR<svg     style="vertical-align:-3.56265pt;width:8.6374998px;" id="M3" height="12.175" version="1.1" viewBox="0 0 8.6374998 12.175" width="8.6374998"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,7.675)"><use xlink:href="#x1D6FE"/></g>

		
	
</svg> mRNA in these cells.  These studies suggest that activation of PPAR<svg     style="vertical-align:-3.56265pt;width:8.6374998px;" id="M4" height="12.175" version="1.1" viewBox="0 0 8.6374998 12.175" width="8.6374998"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,7.675)"><use xlink:href="#x1D6FE"/></g>

		
	
</svg> may modulate cellular oxidative stress.  This paper presents a brief review of recent studies that investigate RPE oxidative stress under various experimental conditions.  This is followed by a detailed review on those reports that examine the protective effect of the natural PPAR<svg     style="vertical-align:-3.56265pt;width:8.6374998px;" id="M5" height="12.175" version="1.1" viewBox="0 0 8.6374998 12.175" width="8.6374998"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,7.675)"><use xlink:href="#x1D6FE"/></g>

		
	
</svg> ligand, 15d-PG<svg     style="vertical-align:-3.27605pt;width:12.05px;" id="M6" height="15.25" version="1.1" viewBox="0 0 12.05 15.25" width="12.05"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,11.112)"><use xlink:href="#x4A"/></g>

			<g transform="matrix(.012,-0,0,-.012,5.65,15.187)"><use xlink:href="#x32"/></g>

		
	
</svg>, against RPE oxidative stress.  This agent can upregulate glutathione and prevent oxidant-induced intracellular reactive oxygen species accumulation, mitochondrial depolarization, and apoptosis. The cytoprotective effect of this agent, however, is not shared by other PPAR<svg     style="vertical-align:-3.56265pt;width:8.6374998px;" id="M7" height="12.175" version="1.1" viewBox="0 0 8.6374998 12.175" width="8.6374998"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,7.675)"><use xlink:href="#x1D6FE"/></g>

		
	
</svg> agonists.  Nonetheless, this property of 15d-PG<svg     style="vertical-align:-3.27605pt;width:12.05px;" id="M8" height="15.25" version="1.1" viewBox="0 0 12.05 15.25" width="12.05"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
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			<g transform="matrix(.012,-0,0,-.012,5.65,15.187)"><use xlink:href="#x32"/></g>

		
	
</svg> may be useful in future development of pharmacological tools against retinal diseases caused by oxidative stress.

Jason Y. Chang

Puran S. Bora

Nalini S. Bora

Prevention of Oxidative Stress-Induced Retinal Pigment Epithelial Cell Death by the PPAR<svg style="vertical-align:-3.56265pt" height="12.175" version="1.1" viewBox="0 0 8.6374998 12.175" width="8.6374998" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg"><g transform="matrix(.017,-0,0,-.017,.062,7.675)"><path id="x1D6FE" d="M478 372q0 -39 -31 -97t-61 -98t-78 -98q-45 -55 -73 -102q-13 -79 -13 -197q-11 -11 -43.5 -25.5t-53.5 -15.5l-15 17q5 35 26 101.5t47 123.5q8 72 -1.5 174.5t-37.5 178.5q-14 37 -29 37q-20 0 -67 -65l-25 21q37 60 73 90.5t63 30.5q47 0 72 -112q13 -56 17.5 -141.5&#xA;t0.5 -143.5h2q155 193 155 297q0 26 -12 47q-5 8 -5 15q0 16 12.5 27t29.5 11q21 0 34 -21t13 -55z"/></g></svg> Agonist, 15-Deoxy-Delta 12, 14-Prostaglandin <svg style="vertical-align:-3.27605pt" height="15.25" version="1.1" viewBox="0 0 12.05 15.25" width="12.05" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg"><g transform="matrix(.017,-0,0,-.017,.062,11.112)"><path id="x4A" d="M303 650v-28q-58 -5 -71.5 -19.5t-13.5 -77.5v-373q0 -99 -18.5 -156.5t-67.5 -102.5q-49 -44 -93 -58l-12 29q78 38 96 130q10 60 10 191v340q0 63 -14 77.5t-75 19.5v28h259z"/></g><g transform="matrix(.012,-0,0,-.012,5.65,15.187)"><path id="x32" d="M412 140l28 -9q0 -2 -35 -131h-373v23q112 112 161 170q59 70 92 127t33 115q0 63 -31 98t-86 35q-75 0 -137 -93l-22 20l57 81q55 59 135 59q69 0 118.5 -46.5t49.5 -122.5q0 -62 -29.5 -114t-102.5 -130l-141 -149h186q42 0 58.5 10.5t38.5 56.5z"/></g></svg>

The uses of highly selective PPAR<svg style="vertical-align:-2.29482pt;width:21.049999px;" id="M2" height="13.55" version="1.1" viewBox="0 0 21.049999 13.55" width="21.049999"  xmlns="http://www.w3.org/2000/svg">
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				<tspan style="font-size: 12.50px; " x="0" y="0">𝛽</tspan>
				<tspan style="font-size: 12.50px; " x="6.9641709" y="0">/</tspan>
				<tspan style="font-size: 12.50px; " x="10.440005" y="0">𝛿</tspan>
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</svg> ligands and PPAR<svg style="vertical-align:-2.29482pt;width:21.049999px;" id="M3" height="13.55" version="1.1" viewBox="0 0 21.049999 13.55" width="21.049999"  xmlns="http://www.w3.org/2000/svg">
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				<tspan style="font-size: 12.50px; " x="0" y="0">𝛽</tspan>
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</svg> knockout mice have shown a direct ability of PPAR<svg style="vertical-align:-2.29482pt;width:21.049999px;" id="M4" height="13.55" version="1.1" viewBox="0 0 21.049999 13.55" width="21.049999"  xmlns="http://www.w3.org/2000/svg">
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</svg> to regulate angiogenesis in vitro and in vivo in animal models. PPAR<svg style="vertical-align:-2.29482pt;width:21.049999px;" id="M5" height="13.55" version="1.1" viewBox="0 0 21.049999 13.55" width="21.049999"  xmlns="http://www.w3.org/2000/svg">
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</svg> ligands induce the proangiogenic growth factor VEGF in many cells and tissues, though its actions in the eye are not known. However, virtually, all tissue components of the eye express PPAR<svg style="vertical-align:-2.29482pt;width:21.049999px;" id="M6" height="13.55" version="1.1" viewBox="0 0 21.049999 13.55" width="21.049999"  xmlns="http://www.w3.org/2000/svg">
	<g transform="matrix(1.25,0,0,-1.25,0,13.55)">
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</svg>. Both angiogenesis and in particular VEGF are not only critical for the development of the retina, but they are also a central component in many common pathologies of the eye, including diabetic retinopathy and age-related macular degeneration, the most common causes of blindness in the Western world. This review, therefore, will discuss the recent evidence of PPAR<svg style="vertical-align:-2.29482pt;width:21.049999px;" id="M7" height="13.55" version="1.1" viewBox="0 0 21.049999 13.55" width="21.049999"  xmlns="http://www.w3.org/2000/svg">
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</svg>-mediated angiogenesis and VEGF release in the context of ocular disorders.

David Bishop-Bailey

A Role for PPAR<svg style="vertical-align:-3.56265pt" height="16.6625" version="1.1" viewBox="0 0 25.7875 16.6625" width="25.7875" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg"><g transform="matrix(.017,-0,0,-.017,.062,12.162)"><path id="x1D6FD" d="M558 587q0 -32 -14 -61t-40 -53.5t-48.5 -41t-54.5 -36.5q144 -51 144 -174q0 -55 -43.5 -108t-104.5 -87q-77 -42 -131 -42q-31 0 -54 20t-31 47l11 18q48 -29 108 -29q79 0 119.5 43t40.5 109t-44.5 107.5t-119.5 50.5l22 47q34 1 65 21q96 61 96 157q0 42 -24 67.5&#xA;t-62 25.5q-24 0 -43.5 -9t-35 -29.5t-27 -44t-22.5 -63t-19.5 -75.5t-18.5 -91q-57 -294 -68 -380q-26 -190 -35 -200q-26 -31 -97 -37l-4 26q19 9 48 170l77 413q23 121 52.5 187.5t83.5 114.5q70 62 148 62q51 0 88.5 -34t37.5 -91z" /></g><g transform="matrix(.017,-0,0,-.017,9.939,12.162)"><path id="x2F" d="M368 703l-264 -866h-60l265 866h59z" /></g><g transform="matrix(.017,-0,0,-.017,16.942,12.162)"><path id="x1D6FF" d="M494 514l-10 -15q-56 76 -106.5 117t-110.5 41q-45 0 -45 -30q0 -28 109 -152q59 -68 86 -118.5t27 -107.5q0 -62 -29.5 -119.5t-86.5 -96.5q-64 -45 -138 -45q-76 0 -121.5 53t-45.5 136q0 74 40.5 135t98.5 95q43 26 87 42q-40 59 -57.5 92t-17.5 62q0 46 39 77.5&#xA;t90 31.5q54 0 97.5 -35.5t65 -78.5t28.5 -84zM359 234q0 84 -90 191q-47 -17 -74 -47q-81 -89 -81 -200q0 -71 32.5 -109.5t72.5 -38.5q47 0 80 33t46.5 77.5t13.5 93.5z" /></g></svg> in Ocular Angiogenesis

The last decade has witnessed an increasing interest for the role played by the peroxisome proliferator-activated receptor-<svg style="vertical-align:-2.34499pt;width:8.0625px;" id="M2" height="9.9375" version="1.1" viewBox="0 0 8.0625 9.9375" width="8.0625"  xmlns="http://www.w3.org/2000/svg">
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				<tspan style="font-size: 12.50px; " x="0" y="0">𝛾</tspan>
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</svg> (PPAR-<svg style="vertical-align:-2.34499pt;width:8.0625px;" id="M3" height="9.9375" version="1.1" viewBox="0 0 8.0625 9.9375" width="8.0625"  xmlns="http://www.w3.org/2000/svg">
	<g transform="matrix(1.25,0,0,-1.25,0,9.9375)">
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</svg>) in controlling inflammation in peripheral organs as well as in the brain. Activation of PPAR-<svg style="vertical-align:-2.34499pt;width:8.0625px;" id="M4" height="9.9375" version="1.1" viewBox="0 0 8.0625 9.9375" width="8.0625"  xmlns="http://www.w3.org/2000/svg">
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</svg> has been shown to control the response of microglial cells, the main macrophage population found in brain parenchyma, and limit the inflammation. The anti-inflammatory capacity of PPAR-<svg style="vertical-align:-2.34499pt;width:8.0625px;" id="M5" height="9.9375" version="1.1" viewBox="0 0 8.0625 9.9375" width="8.0625"  xmlns="http://www.w3.org/2000/svg">
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</svg> agonists  has led to the hypothesis that PPAR-<svg style="vertical-align:-2.34499pt;width:8.0625px;" id="M6" height="9.9375" version="1.1" viewBox="0 0 8.0625 9.9375" width="8.0625"  xmlns="http://www.w3.org/2000/svg">
	<g transform="matrix(1.25,0,0,-1.25,0,9.9375)">
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</svg> might be targeted to modulate  degenerative brain diseases in which inflammation has been increasingly recognized as a significant component. Recent experimental evidence suggests  that PPAR-<svg style="vertical-align:-2.34499pt;width:8.0625px;" id="M7" height="9.9375" version="1.1" viewBox="0 0 8.0625 9.9375" width="8.0625"  xmlns="http://www.w3.org/2000/svg">
	<g transform="matrix(1.25,0,0,-1.25,0,9.9375)">
		<g transform="translate(72,-64.05)">
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				<tspan style="font-size: 12.50px; " x="0" y="0">𝛾</tspan>
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</svg> agonists could be exploited to treat ocular diseases such as diabetic retinopathy, age-related macular degeneration, autoimmune uveitis, and optic neuritis where inflammation  has relevant role. Additional  PPAR-<svg style="vertical-align:-2.34499pt;width:8.0625px;" id="M8" height="9.9375" version="1.1" viewBox="0 0 8.0625 9.9375" width="8.0625"  xmlns="http://www.w3.org/2000/svg">
	<g transform="matrix(1.25,0,0,-1.25,0,9.9375)">
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				<tspan style="font-size: 12.50px; " x="0" y="0">𝛾</tspan>
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</svg> agonist beneficial effects could involve amelioration of retinal microcirculation and inhibition of neovascularization. However,  PPAR-<svg style="vertical-align:-2.34499pt;width:8.0625px;" id="M9" height="9.9375" version="1.1" viewBox="0 0 8.0625 9.9375" width="8.0625"  xmlns="http://www.w3.org/2000/svg">
	<g transform="matrix(1.25,0,0,-1.25,0,9.9375)">
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				<tspan style="font-size: 12.50px; " x="0" y="0">𝛾</tspan>
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</svg> activation could, in some instances,  aggravate the ocular pathology, for example, by increasing the synthesis of vascular endothelial growth factor, a proangiogenic factor that could trigger a vicious circle and further deteriorate retinal perfusion. The development of new in vivo and in vitro models to study ocular inflammation and how to modulate for the eye benefit will be instrumental for the search of  effective therapies.

Fiorella Malchiodi-Albedi

Andrea Matteucci

Antonietta Bernardo

Luisa Minghetti

PPAR-<svg style="vertical-align:-3.56265pt" height="12.175" version="1.1" viewBox="0 0 8.6374998 12.175" width="8.6374998" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg"><g transform="matrix(.017,-0,0,-.017,.062,7.675)"><path id="x1D6FE" d="M478 372q0 -39 -31 -97t-61 -98t-78 -98q-45 -55 -73 -102q-13 -79 -13 -197q-11 -11 -43.5 -25.5t-53.5 -15.5l-15 17q5 35 26 101.5t47 123.5q8 72 -1.5 174.5t-37.5 178.5q-14 37 -29 37q-20 0 -67 -65l-25 21q37 60 73 90.5t63 30.5q47 0 72 -112q13 -56 17.5 -141.5&#xA;t0.5 -143.5h2q155 193 155 297q0 26 -12 47q-5 8 -5 15q0 16 12.5 27t29.5 11q21 0 34 -21t13 -55z" /></g></svg>, Microglial Cells, and Ocular Inflammation: New Venues for Potential Therapeutic Approaches

Thyroid eye disease (TED) is an autoimmune condition in which intense inflammation leads to orbital tissue remodeling, including the accumulation of extracellular macromolecules and fat. Disease progression depends upon interactions between lymphocytes and orbital fibroblasts. These cells engage in a cycle of reciprocal activation which produces the tissue characteristics of TED. Peroxisome proliferator-activated receptor-<svg style="vertical-align:-2.34499pt;width:8.0625px;" id="M2" height="9.9375" version="1.1" viewBox="0 0 8.0625 9.9375" width="8.0625"  xmlns="http://www.w3.org/2000/svg">
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</svg> (PPAR<svg style="vertical-align:-2.34499pt;width:8.0625px;" id="M3" height="9.9375" version="1.1" viewBox="0 0 8.0625 9.9375" width="8.0625"  xmlns="http://www.w3.org/2000/svg">
	<g transform="matrix(1.25,0,0,-1.25,0,9.9375)">
		<g transform="translate(72,-64.05)">
			<text transform="matrix(1,0,0,-1,-71.95,66.44)">
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</svg>) may play divergent roles in this process, both attenuating and promoting disease progression. PPAR<svg style="vertical-align:-2.34499pt;width:8.0625px;" id="M4" height="9.9375" version="1.1" viewBox="0 0 8.0625 9.9375" width="8.0625"  xmlns="http://www.w3.org/2000/svg">
	<g transform="matrix(1.25,0,0,-1.25,0,9.9375)">
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				<tspan style="font-size: 12.50px; " x="0" y="0">𝛾</tspan>
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</svg> has anti-inflammatory activity, suggesting that it could interrupt intercellular communication. However, PPAR<svg style="vertical-align:-2.34499pt;width:8.0625px;" id="M5" height="9.9375" version="1.1" viewBox="0 0 8.0625 9.9375" width="8.0625"  xmlns="http://www.w3.org/2000/svg">
	<g transform="matrix(1.25,0,0,-1.25,0,9.9375)">
		<g transform="translate(72,-64.05)">
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				<tspan style="font-size: 12.50px; " x="0" y="0">𝛾</tspan>
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</svg> activation is also critical to adipogenesis, making it a potential culprit in the pathological fat accumulation associated with TED. This review explores the role of PPAR<svg style="vertical-align:-2.34499pt;width:8.0625px;" id="M6" height="9.9375" version="1.1" viewBox="0 0 8.0625 9.9375" width="8.0625"  xmlns="http://www.w3.org/2000/svg">
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</svg> in TED, as it pertains to crosstalk between lymphocytes and fibroblasts and the development of therapeutics targeting cell-cell interactions mediated through this signaling pathway.

G. M. Lehmann

T. M. Garcia-Bates

T. J. Smith

S. E. Feldon

R. P. Phipps

Regulation of Lymphocyte Function by PPAR<svg style="vertical-align:-3.56265pt" height="12.175" version="1.1" viewBox="0 0 8.6374998 12.175" width="8.6374998" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg"><g transform="matrix(.017,-0,0,-.017,.062,7.675)"><path id="x1D6FE" d="M478 372q0 -39 -31 -97t-61 -98t-78 -98q-45 -55 -73 -102q-13 -79 -13 -197q-11 -11 -43.5 -25.5t-53.5 -15.5l-15 17q5 35 26 101.5t47 123.5q8 72 -1.5 174.5t-37.5 178.5q-14 37 -29 37q-20 0 -67 -65l-25 21q37 60 73 90.5t63 30.5q47 0 72 -112q13 -56 17.5 -141.5&#xA;t0.5 -143.5h2q155 193 155 297q0 26 -12 47q-5 8 -5 15q0 16 12.5 27t29.5 11q21 0 34 -21t13 -55z" /></g></svg>: Relevance to Thyroid Eye Disease-Related Inflammation

The retinal vessels have two barriers: the retinal pigment epithelium and the retinal vascular endothelium. Each barrier exhibits increased permeability under various pathological conditions. This condition is referred to as blood retinal barrier (BRB) breakdown. Clinically, the most frequently encountered condition causing BRB breakdown is diabetic retinopathy. In recent studies, inflammation has been linked to BRB breakdown and vascular leakage in diabetic retinopathy. Biological support for the role of inflammation in early diabetes is the adhesion of leukocytes to the retinal vasculature (leukostasis) observed in diabetic retinopathy. <svg style="vertical-align:-2.34499pt;width:46.262501px;" id="M2" height="13.575" version="1.1" viewBox="0 0 46.262501 13.575" width="46.262501"  xmlns="http://www.w3.org/2000/svg">
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			</text>

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				<tspan style="font-size: 12.50px; " x="0" y="0">𝛾</tspan>
			</text>

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</svg> is a member of a ligand-activated nuclear receptor superfamily and plays a critical role in a variety of biological processes, including adipogenesis, glucose metabolism, angiogenesis, and inflammation. There is now strong experimental evidence to support the theory that <svg style="vertical-align:-2.34499pt;width:46.262501px;" id="M3" height="13.575" version="1.1" viewBox="0 0 46.262501 13.575" width="46.262501"  xmlns="http://www.w3.org/2000/svg">
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				<tspan style="font-size: 12.50px; " x="0" y="0">𝛾</tspan>
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</svg> inhibits diabetes-induced retinal leukostasis and leakage, playing an important role in the pathogenesis of diabetic retinopathy. Therapeutic targeting of <svg style="vertical-align:-2.34499pt;width:46.262501px;" id="M4" height="13.575" version="1.1" viewBox="0 0 46.262501 13.575" width="46.262501"  xmlns="http://www.w3.org/2000/svg">
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</svg> may be beneficial to diabetic retinopathy.

Yasuo Yanagi

Role of Peroxisome Proliferator Activator Receptor <svg style="vertical-align:-3.56265pt" height="12.175" version="1.1" viewBox="0 0 8.6374998 12.175" width="8.6374998" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg"><g transform="matrix(.017,-0,0,-.017,.062,7.675)"><path id="x1D6FE" d="M478 372q0 -39 -31 -97t-61 -98t-78 -98q-45 -55 -73 -102q-13 -79 -13 -197q-11 -11 -43.5 -25.5t-53.5 -15.5l-15 17q5 35 26 101.5t47 123.5q8 72 -1.5 174.5t-37.5 178.5q-14 37 -29 37q-20 0 -67 -65l-25 21q37 60 73 90.5t63 30.5q47 0 72 -112q13 -56 17.5 -141.5&#xA;t0.5 -143.5h2q155 193 155 297q0 26 -12 47q-5 8 -5 15q0 16 12.5 27t29.5 11q21 0 34 -21t13 -55z" /></g></svg> on Blood Retinal Barrier Breakdown

Age-related macular degeneration (AMD) is the leading cause 
    of new blindness in the western world and is becoming more of 
    a socio-medical problem as the proportion of the aged 
    population increases.  There are multiple efforts underway to 
    better understand this disease process.  AMD involves the 
    abnormal retinal pigment epithelium (RPE), drusen formation, 
    photoreceptor atrophy, and choroidal neovascularization.  
    Peroxisome proliferator-activated receptors (PPARs) play an 
    important role in lipid degeneration, immune regulation, 
    regulation of reactive oxygen species (ROSs), as well as 
    regulation of vascular endothelial growth factor (VEGF), 
    matrix metalloproteinase-9 (MMP-9), and 
    docosahexaenoic acid (DHA).   These molecules have all been 
    implicated in the pathogenesis of AMD.  In addition, PPAR 
    gamma is expressed in RPE, an essential cell in photoreceptor 
    regeneration and vision maintenance.  This review summarizes 
    the interactions between PPAR, AMD-related molecules, and 
    AMD-related disease processes.

Alexandra A. Herzlich

Jingsheng  Tuo

Chi-Chao  Chan

Peroxisome Proliferator-Activated Receptor and Age-Related Macular Degeneration

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<p><em>PPAR Research</em> publishes articles related to mechanisms involved in the activation of peroxisome proliferator-activated receptors, as well as their role in regulation of cellular differentiation, development, energy homeostasis and metabolic function.</p>


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<p>Chief Editor, Dr Xiao-Jie Lu, is dedicated to basic and translational research on liver diseases. His research at Nanjing Medical University, China, focuses&nbsp;on exploring these diseases' underlying mechanisms that may be translatable to novel diagnostic biomarkers or therapeutic targets.</p>


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PPAR Research publishes articles related to mechanisms involved in the activation of peroxisome proliferator-activated receptors, as well as their role in regulation of cellular differentiation, development, energy homeostasis and metabolic function.

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PPAR Research

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PPAR Research

PPARs in Eye Biology and Disease

PPARs in Eye Biology and Disease

Articles

PPARs in Eye Biology and Disease

PPAR Agonists: Potential as Therapeutics for Neovascular Retinopathies

PPAR- Ligands as Potential Therapeutic Agents for Wet Age-Related Macular Degeneration

Prevention of Oxidative Stress-Induced Retinal Pigment Epithelial Cell Death by the PPAR Agonist, 15-Deoxy-Delta 12, 14-Prostaglandin

A Role for PPAR in Ocular Angiogenesis

PPAR-, Microglial Cells, and Ocular Inflammation: New Venues for Potential Therapeutic Approaches

Regulation of Lymphocyte Function by PPAR: Relevance to Thyroid Eye Disease-Related Inflammation

Role of Peroxisome Proliferator Activator Receptor on Blood Retinal Barrier Breakdown

Peroxisome Proliferator-Activated Receptor and Age-Related Macular Degeneration