Vitreous Of Proliferative Diabetic Retinopathy Patients Research Articles

OR2806 Levosulpiride-Induced Hyperprolactinemia For The Treatment Of Diabetic Macular Edema: A Phase 2 Pilot Clinical Trial

Abstract Disclosure: C. Clapp: None. C.D. Núñez-Amaro: None. M. López: None. E. Adán-Castro: None. M. Robles Osorio: None. R. García-Franco: None. M. García-Roa: None. Y. Villalpando: None. P. Ramírez-Neria: None. N. Pineiro: None. J.F. Rubio-Mijangos: None. J. Sánchez: None. G. Ramirez-Hernandez: None. L. Siqueiros-Márquez: None. N. Díaz-Lezama: None. E. López-Star: None. T. Bertsch: None. G. Martínez de la Escalera: None. J. Triebel: None. Vasoinhibin is a fragment of prolactin that inhibits the permeability and growth of blood vessels. The prokinetic dopamine D2 receptor blocker, levosulpiride, elevates the circulating levels of prolactin and the accumulation of vasoinhibin in the vitreous of patients with proliferative diabetic retinopathy (PDR) (1) suggesting clinical benefits due to the vascular properties of vasoinhibin. Here, we describe the 2-month results of a phase 2 clinical trial (2) investigating the biological activity of levosulpiride in center-involving diabetic macular edema (DME). This prospective, randomized, double-masked, dual-center, placebo-controlled, pilot study was carried out in individuals (aged 40 to 69 years) with DME involving the center of the macula and best-corrected visual acuity (BCVA) between 58 and 16 ETDRS letters at 4 m (20/16 to 20/100 Snellen equivalent) or with PDR undergoing elective pars plana vitrectomy. Oral treatment (TID) with levosulpiride or placebo was for 8 weeks in DME patients or for the 1 week before vitrectomy in PDR patients. Primary outcome measures included changes from baseline in BCVA, central foveal thickness (CFT), and mean macular volume (MMV) every 2 weeks for 8 weeks in placebo- (17 patients, 18 eyes) and levosulpiride- (17 patients, 22 eyes) treated DME groups; whereas vitreous levels of vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) were primary outcomes in PDR patients after placebo (18 patients) or levosulpiride (18 patients). Starting at 4 weeks, levosulpiride improved changes from baseline in BCVA (P < 0.037), CFT (P < 0.013), and MMV (P < 0.002) compared to placebo. At 8 weeks, the proportion of eyes gaining >5 letters (41% vs. 28%), loosing > 21 μm in CFT (55% vs. 28%), and dropping > 0.06 mm3 in MMV (65% vs. 29%) were higher in levosulpiride vs placebo. The overall grading of visual (BCVA) and structural parameters (CFT, MMV, OCT macula image, fundoscopy, and fluorescein angiography) showed improvement with levosulpiride (P = 0.029). Levosulpiride reduced VEGF (P = 0.025) and PlGF (P= 0.008) levels in the vitreous of PDR patients. There were no apparent adverse side-effects. In conclusion, oral levosulpiride administration for 8 weeks improved visual and structural outcomes in patients with center involving DME by mechanisms that may include intraocular upregulation of vasoinhibin and downregulation of VEGF and PlGF. Larger clinical trials evaluating long-term efficacy and safety are warranted. Reference: (1) Núñez-Amaro et al., Transl Vis Sci Technol. 2020 Aug 17;9(9):27. (2) www.clinicaltrials.gov, ID: NCT03161652; Supported by UNAM grant 405PC. Presentation: Sunday, June 18, 2023

Levosulpiride for the treatment of diabetic macular oedema: a phase 2 randomized clinical trial

Background/ObjectiveThe prokinetic levosulpiride elevates vasoinhibin levels in the vitreous of patients with proliferative diabetic retinopathy (PDR) suggesting clinical benefits due to the anti-vasopermeability and anti-angiogenic properties of vasoinhibin. We investigated the biological activity of levosulpiride in centre-involving diabetic macular oedema (DME).Patients/MethodsProspective, randomized, double-blinded, dual-centre, phase 2 trial in patients with centre-involving DME orally treated with placebo (n = 17) or levosulpiride (n = 17) for 8 weeks or in patients with PDR undergoing elective pars plana vitrectomy and receiving placebo (n = 18) or levosulpiride (n = 18) orally for the 1 week before vitrectomy.ResultsLevosulpiride improved changes from baseline in best-corrected visual acuity (p ≤ 0.037), central foveal thickness (CFT, p ≤ 0.013), and mean macular volume (MMV, p ≤ 0.002) at weeks 4, 6, and 8 compared to placebo. At 8 weeks, the proportion of eyes gaining ≥5 ETDRS letters at 4 m (41% vs. 28%), losing ≥21 μm in CFT (55% vs. 28%), and dropping ≥0.06 mm3 in MMV (65% vs. 29%) was higher after levosulpiride than placebo. The overall grading of visual and structural parameters improved with levosulpiride (p = 0.029). Levosulpiride reduced VEGF (p = 0.025) and PlGF (p = 0.008) levels in the vitreous of PDR patients. No significant adverse side-effects were detected.ConclusionsOral levosulpiride for 8 weeks improved visual and structural outcomes in patients with centre-involving DME by mechanisms that may include intraocular upregulation of vasoinhibin and downregulation of VEGF and PlGF. Larger clinical trials evaluating long-term efficacy and safety are warranted.

Elevated NLRP3 Inflammasome Levels Correlate With Vitamin D in the Vitreous of Proliferative Diabetic Retinopathy.

Purpose: This study aims to determine vitamin D concentrations in the vitreous and serum, as well as the expression levels of NLRP3 inflammasome pathway in the vitreous of patients with proliferative diabetic retinopathy (PDR). In addition, we investigated the possible correlation between NLRP3 inflammasome levels and vitamin D concentrations.Methods: We obtained vitreous samples before vitrectomy from 55 PDR patients, 25 non-diabetic patients with idiopathic macular hole (IMH), and 10 non-proliferative diabetic retinopathy (NPDR) patients. We also collected serum samples from the same patients. Enzyme-linked immunosorbent assay (ELISA) was used to examine NLRP3 inflammasome pathway proteins, including NLRP3, caspase-1, IL-1β, and VEGF. In addition, vitamin D concentrations were analyzed in Roche Cobas 6000's module e601 platform using electrochemiluminescence immune assay.Results: The levels of NLRP3 inflammasome pathway and VEGF increased dramatically in PDR vitreous. However, vitamin D concentrations in vitreous and serum followed the opposite trend. Meanwhile, vitreous and serum vitamin D concentrations were significantly negatively correlated with vitreous NLRP3 expression in PDR patients. Moreover, serum and vitreous vitamin D concentrations were positively correlated and demonstrated discriminatory ability in DR. The subgroup analysis of PDR group revealed that eyes with tractional retinal detachment (TRD) had higher NLRP3 inflammasome pathway and VEGF levels but lower vitamin D concentrations. Conversely, eyes that received preoperative pan-retinal photocoagulation (PRP) exhibited lower levels of NLRP3 inflammasome pathway, but vitamin D concentrations were irrelevant to laser treatment.Conclusions: Our results demonstrate a strong correlation between increased NLRP3 inflammasome pathway and decreased vitamin D concentrations in the vitreous of PDR patients, which may be linked to PDR pathogenesis. In addition, vitamin D supplementation may play a key role in preventing, treating, and improving PDR prognosis due to its inhibitory impact on NLRP3 inflammasome pathway and VEGF.

PDGF as an Important Initiator for Neurite Outgrowth Associated with Fibrovascular Membranes in Proliferative Diabetic Retinopathy

ABSTRACT Purpose The formation of fibrovascular membranes (FVMs) is a serious sight-threatening complication of proliferative diabetic retinopathy (PDR) that may result in retinal detachment and eventual blindness. During the formation of these membranes, neurite/process outgrowth occurs in retinal neurons and glial cells, which may both serve as a scaffold and have guiding or regulatory roles. To further understand this process, we investigated whether previously identified candidate proteins, from vitreous of PDR patients with FVMs, could induce neurite outgrowth in an experimental setting. Materials and methods Retinal explants of C57BL6/N mouse pups on postnatal day 3 (P3) were cultured in poly-L-lysine- and laminin-coated dishes. Outgrowth stimulation experiments were performed with the addition of potential inducers of neurite outgrowth. Automated analysis of neurite outgrowth was performed by measuring β–tubulin-immunopositive neurites using Image J. Expression of PDGF receptors was quantified by RT-PCR in FVMs of PDR patients. Results Platelet-derived growth factor (PDGF) induced neurite outgrowth in a concentration-dependent manner, whilst neuregulin 1 (NRG1) and connective tissue growth factor (CTGF) did not. When comparing three different PDGF dimers, treatment with PDGF-AB resulted in the highest neurite induction, followed by PDGF-AA and -BB. In addition, incubation of retinal explants with vitreous from PDR patients resulted in a significant induction of neurite outgrowth as compared to non-diabetic control vitreous from patients with macular holes, which could be prevented by addition of CP673451, a potent PDGF receptor (PDGFR) inhibitor. Abundant expression of PDGF receptors was detected in FVMs. Conclusion Our findings suggest that PDGF may be involved in the retinal neurite outgrowth, which is associated with the formation of FVMs in PDR.

Decreased Presence of Mast Cells in the Bursa Premacularis of Proliferative Diabetic Retinopathy

Introduction: We previously reported that the intravitreal activities of chymase and tryptase were more increased in the patients with macular hole (MH) and epiretinal membrane (ERM) than in those with proliferative diabetic retinopathy (PDR) and that the source of these serine proteases might be mast cells in the bursa premacularis (BPM). The purpose of this study was to compare the density of mast cells in BPM samples obtained from MH, ERM, and PDR patients. Methods: BPM and vitreous core samples were first collected during vitrectomy from eyes afflicted with vitreoretinal diseases (MH: 6 eyes, ERM: 3 eyes, and PDR: 9 eyes), and then were stained with hematoxylin, toluidine blue, antibodies against chymase and tryptase, and a terminal deoxynucleotidyl transferase dUTP nick end labeling assay kit. Results: Hematoxylin nuclear staining showed fewer positive-staining cells in the BPM samples obtained from PDR patients than in those obtained from MH and ERM patients. Toluidine blue staining of the BPM revealed metachromasia in the mast cells of the patients with MH and ERM, but not those of the patients with PDR. In addition, immunostaining using anti-chymase and anti-tryptase antibodies showed that the BPM samples were more intensely stained than the vitreous core samples from the patients with MH and ERM and that both tissue samples were poorly stained in the patients with PDR. The apoptotic cells were more frequently observed in the BPM samples from patients with MH than in those from patients with PDR. Conclusions: These findings indicated that lower activities of chymase and tryptase in the vitreous of PDR patients appeared to be attributable to the decreased presence of mast cells in the BPM. The lack of mast cells in the BPM might be related to the pathogenesis of PDR.

MicroRNA Expression Profile in the Vitreous of Proliferative Diabetic Retinopathy Patients and Differences from Patients Treated with Anti-VEGF Therapy

PurposemicroRNAs (miRNAs) mediate the pathological mechanisms of diabetic retinopathy. In this study, we compared miRNA expression profiles in the vitreous between patients with proliferative diabetic retinopathy (PDR) and patients with a macular hole as non-diabetic controls, and between PDR patients treated with anti-vascular endothelial growth factor (VEGF) therapy and untreated PDR patients.MethodsVitreous samples of non-diabetic and PDR patients were screened for miRNAs with quantitative polymerase chain reaction (qPCR) panels. miRNA candidates were validated in vitreous samples of a second, independent cohort. In addition, the effect of anti-VEGF therapy was investigated in the vitreous of a third study population consisting of PDR patients who had not received anti-VEGF therapy and PDR patients who had received preoperative anti-VEGF therapy.ResultsDuring screening, seven miRNAs were found to be significantly higher in the vitreous of PDR patients, whereas two miRNAs were found to be significantly lower compared with non-diabetic controls. Validating the expression of these miRNAs in a second cohort resulted in the identification of six miRNAs that were expressed at significantly higher rates in the vitreous of PDR patients: hsa-miR-20a-5p, hsa-miR-23b-3p, hsa-miR-142-3p, hsa-miR-185-5p, hsa-miR-326, and hsa-miR-362-5p. Among these six miRNAs, hsa-miR-23b-3p levels were lower in the anti-VEGF-treated group of PDR patients compared with untreated PDR patients.ConclusionsIn this study, we identified six miRNAs that are expressed more highly in PDR patients and one miRNA that is expressed at a lower levels in anti-VEGF-treated PDR patients.Translational RelevancemiRNAs identified in the vitreous of PDR patients may improve our understanding of the mechanisms leading to PDR.

A Systematic Investigation on Complement Pathway Activation in Diabetic Retinopathy

The complement system plays a crucial role in retinal homeostasis. While the proteomic analysis of ocular tissues in diabetic retinopathy (DR) has shown the deposition of complement proteins, their exact role in the pathogenesis of DR is yet unclear. We performed a detailed investigation of the role of the complement system by evaluating the levels of major complement proteins including C3, C1q, C4b, Complement Factor B (CFB), and Complement Factor H (CFH) and their activated fragments from both the classical and alternative pathways in vitreous humor and serum samples from proliferative DR (PDR) patients and controls. Further, the expressions of complements and several other key pro- and anti-angiogenic genes in the serum and vitreous humor were analyzed in the blood samples of PDR and non-PDR (NPDR) patients along with controls without diabetes. We also assessed the pro-inflammatory cytokines and matrix metalloproteinases in the vitreous humor samples. There was a significant increase in C3 and its activated fragment C3bα' (110 kDa) along with a corresponding upregulation of CFH in the vitreous of PDR patients, which confirmed the increased activation of the alternative complement pathway in PDR. Likewise, a significant upregulation of angiogenic genes and downregulation of anti-angiogenic genes was seen in PDR and NPDR cases. Increased MMP9 activity and upregulation of inflammatory markers IL8 and sPECAM with a downregulation of anti-inflammatory marker IL-10 in PDR vitreous indicated the possible involvement of microglia in DR pathogenesis. Further, a significantly high C3 deposition in the capillary wall along with thickening of basement membranes and co-localization of CFH expression with CD11b+ve activated microglial cells in diabetic retina suggested microglia as a source of CFH in diabetic retina. The increased CFH levels could be a feedback mechanism for arresting excessive complement activation in DR eyes. A gradual increase of CFH and CD11b expression in retina with early to late changes in epiretinal membranes of DR patients indicated a major role for the alternative complement pathway in disease progression.

Diabetes-induced oxidative stress in the vitreous humor

PurposeDiabetes is accompanied by fundamental rearrangements in redox homeostasis. Hyperglycemia triggers the production of reactive oxygen and nitrogen species which contributes to tissue damage in various target organs. Proliferative diabetic retinopathy (PDR) is a common manifestation of diabetic complications but information on the possible role of reactive intermediates in this condition with special regard to the involvement of the vitreous in PDR-associated redox alterations is scarce.The aim of the study was to determine key parameters of redox homeostasis [advanced glycation endproducts (AGE); protein carbonyl and glutathione (GSH)] content in the vitreous in PDR patients. MethodsThe study population involved 10 diabetic patients undergoing surgery for complications of proliferative diabetic retinopathy and 8 control (non-diabetic) patients who were undergoing surgery for epiretinal membranes. Vitreal fluids were assayed for the above biochemical parameters. ResultsWe found elevated levels of AGE in the vitreous of PDR patients (812.10 vs 491.69ng AGE/mg protein). Extent of protein carbonylation was also higher in the samples of diabetic patients (2.08 vs 0.67A/100μg protein). The GSH content also increased in the vitreous of PDR patients as compared to the control group (4.54 vs 2.35μmol/μg protein), respectively. ConclusionThe study demonstrates that diabetes-associated redox alterations also reach the vitreous with the most prominent changes being increased protein carbonylation and increased antioxidant levels.

Evaluation of T‐cell related cytokines in the vitreous of proliferative diabetic retinopathy

SummaryMacrophages are involved in low‐grade inflammation in diabetes, and play pathogenic roles in proliferative diabetic retinopathy (PDR) by producing proinflammatory cytokines. T cells as well as other cells are activated by proinflammatory cytokines, and the infiltration into the vitreous of patients with PDR has been shown. We have recently found that both positive rates and levels of IL4, IL‐6, IL‐10, IL‐17A, IL‐21, IL‐22, and TNFα in the vitreous of PDR patients were significantly higher than those in the serum, and that vitreous levels of these cytokines and IL‐31 were significantly higher in PDR patients than in epiretinal membrane or macular hole patients. In addition, although vitreous of IFN‐g and sCD40L in the vitreous of endogenous uveitis (EU) patients were significantly higher than those of PDR patients, vitreous levels of IL‐4, IL‐17A, IL‐22, IL‐31, and TNFa were conversely higher in the vitreous of PDR patients than those of EU patients. Although it is unclear whether these cytokines synergistically play facilitative roles or inhibitory roles for the progression of PDR, our study suggested that Th2‐ and Th17‐related immune responses are involved in the pathogenesis of PDR.

The correlation study of the expression of VEGF with t-PA and PAI expression in plasma and intraocular tissue in proliferative diabetic retinopathy

To evaluate the correlation between the expression of VEGF with t-PA and PAI expression in plasma aqueous humor and vitreous of proliferative diabetic retinopathy (PDR). It was an experimental study. The concentrations of VEGF t-PA and PAI in plasma, aqueous humor and vitreous body in PDR and normal group were detected by ELISA. The levels of VEGF (53.37 ng/L) and PAI (8.00 µg/L) in the plasma of PDR patients were higher than control group, and there was significant statistically difference between them (Z = -3.437, -5.816; P < 0.01). The levels of t-PA (24.32 µg/L) in plasma of PDR patients and control group was no statistically difference between them (Z = -1.715, P = 0.086). The levels of VEGF (335.00 ng/L) t-PA (5.70 µg/L) and PAI (0.63 µg/L) in the aqueous humor of PDR patients were higher than control group, and there was statistically difference between them (Z = -4.805, -1.967, -4.018; P < 0.05). The levels of VEGF (691.69 ng/L) t-PA (13.05 µg/L) and PAI (4.01 µg/L) in the vitreous of PDR patients were higher than control group , and there was statistically difference between them (Z = -2.807, -2.642, -2.230;P < 0.05). Compare the plasma aqueous humor and vitreous of PDR patients. The levels of VEGF is: vitreous>aqueous humor>plasma. The levels of t-PA is: plasma>vitreous>aqueous humor. The levels of PAI is: plasma and vitreous>aqueous humor. The expression of VEGF was highly correlated with t-PA and PAI in plasma aqueous humor and vitreous of PDR (P < 0.05). VEGF PAI in plasma, VEGF t-PA PAI in aqueous humor and vitreous were increases. The expression of VEGF was positive correlated with t-PA and PAI in plasma aqueous humor and vitreous of PDR.

Roles of elevated intravitreal IL-1β and IL-10 levels in proliferative diabetic retinopathy.

Purpose:To determine the roles of interleukin (IL)-1β and IL-10 in the vitreous of proliferative diabetic retinopathy (PDR).Materials and Methods:Vitreous samples were obtained from 26 eyes of 26 patients with PDR and from eight eyes of eight cases without PDR. The IL-1β and IL-10 concentration in the vitreous was measured by using an enzyme-linked immunosorbent assay (ELISA).Results:Levels of IL-1β and IL-10 in vitreous were higher in PDR patients compared with control group. And there was significantly negative correlation between IL-1β and IL-10 in control group (r = −0.795; P = 0.032), whereas there was no significant correlation in PDR group (r = 0.176; P = 0.391).Conclusion:Levels of IL-1β and IL-10 were upregulated in vitreous of PDR patients, and these two cytokines play roles in regulating the development and progression of PDR.

Role of Intravitreal Inflammatory Cytokines and Angiogenic Factors in Proliferative Diabetic Retinopathy

Objective: Inflammatory reaction has been shown to involve the progress of type 2 (non-insulin-dependent) diabetes. We, therefore, examined the effects of inflammatory cytokines and angiogenic factors in the pathogenesis of proliferative diabetic retinopathy (PDR) in type 2 diabetes.Patients and methods: Vitreous fluid samples were obtained by vitrectomy from 62 eyes of PDR patients with type 2 diabetes and from 20 eyes of age-matched non-diabetic patients. The concentrations of interleukin 1 beta (IL1B), IL6, IL8, IL10, chemokine (C-C motif) ligand 2 (CCL2), endothelin 1 (EDN1), vascular endothelial growth factor (VEGF), and tumor necrosis factor (TNF) in the vitreous samples were measured by enzyme-linked immunosorbent assay (ELISA).Results: The concentrations of LI1B, IL6, IL8, CCL2, EDN1, VEGF, and TNF in the vitreous samples were considerably higher in PDR patients in comparison with the controls. However, the level of IL10 in PDR patients was similar to that obtained in the controls. Analysis of the correlations of the studied factors revealed the correlation of VEGF and IL6, VEGF and EDN1, IL8 and CCL2, and EDN1 and TNF in PDR patients. In addition, a significant positive correlation was observed between vitreous TNF as well as EDN1 and serum HbA1c levels in PDR patients.Conclusions: The inflammatory cytokines and angiogenic factors IL1B, IL6, IL8, CCL2, EDN1, VEGF, and TNF are increased in the vitreous of PDR patients without an increase in IL-10. These results add support to the role of inflammatory cytokines and angiogenic factors in the genesis of PDR. Understanding the implication of these cytokines may provide diagnostic tools and therapeutic targets for treatment and prevention of PDR.

Intravitreous high expression level of netrin-1 in patients with proliferative diabetic retinopathy.

To investigate the significance of netrin-1 and vascular endothelial growth factor (VEGF) in the pathogenesis of retinal angiogenesis, the levels of netrin-1 and VEGF in the vitreous fluid and serum of the proliferative diabetic retinopathy (PDR) and non-proliferative diabetic retinopathy (non-PDR) patients were measured. We then determined the netrin-1 and VEGF expression in the oxygen induced retinopathy (OIR) mice retinas. A total of 18 eyes from 18 patients were included in our study and 10 of them were collected from PDR patients and 8 from non-PDR patients. Undiluted vitreous fluid samples were collected during pars plana vitrectomy. Appropriate blood samples were collected if possible. Netrin-1 and VEGF levels in the vitreous fluid and plasma were determined by Enzyme-linked Immunosorbent Assays. OIR mice models were established, and netrin-1 and VEGF levels were determined by immunohistochemistry analysis. The levels of netrin-1 and VEGF in the vitreous of PDR patients were significantly higher than those in the controls (Mediannetrin-1=509.94 vs. 85.91 pg/ml, P<0.001 and Median VEGF=762.60 vs. 77.52 pg pg/ml, P<0.001). Netrin-1 was mainly expressed in GCL and INL of the retina in mice. Both netrin-1 and VEGF were up-regulated in OIR mice. Netrin-1 and VEGF levels were elevated in vitreous fluid of the PDR patients and the OIR mice retinas. Therefore, netrin-1 may play important roles in pathological retinal angiogenesis.

Effect of retinal laser photocoagulation on the activity of metalloproteinases and the α2-Macroglobulin proteolytic state in the vitreous of eyes with proliferative diabetic retinopathy

Panretinal photocoagulation (PRP) reduces the incidence of severe visual loss in proliferative diabetic retinopathy (PDR). The aim of the study was to determine the effect of PRP on the activity of matrix metalloproteinase-2 (MMP-2) and MMP-9, and also on the α2-Macroglobulin (α2M) proteolytic state in the vitreous of eyes with PDR. Vitreous samples were obtained from patients undergoing vitrectomy for the treatment of retinal diseases: 17 with PDR and eight with idiopathic macular hole (MH). Qualitative evaluation of the MMP-2 and MMP-9 activation status was performed by gelatin zymography and quantitative assay was carried out for vitreous total protein content and α2M. The proteolytic state of α2M was evaluated by Western blotting. Although all vitreous samples contained proMMP-2, increased proMMP-9 and active MMP-9 were detected in PDR samples without PRP. In addition, after PRP the proMMP-9 activity was significantly decreased, whereas the proMMP-2 activity was not affected. Enhanced total protein and α2M concentrations were observed in all vitreous samples from PDR patients with and without previous PRP compared with samples from patients with MH. However, a differential proteolytic state of α2M, expressed as 180/85–90kDa ratio, was detected among PDR patients with and without PRP treatment. Whereas a low 180/85–90kDa ratio of α2M in vitreous of PDR patients without PRP was observed, a high proportion of 180kDa subunit was principally detected in PDR with PRP. These results demonstrate that PDR occurs with an enhanced activity of MMP-9 and activation of α2M by proteinases, which is reversed after PRP. In addition, we suggest that α2M plays a key role in the control and regulation of the ocular neovascularization involved in the pathogenesis of ischemic retinal diseases such as PDR.

Macrophage migration inhibitory factor levels in the vitreous of patients with proliferative diabetic retinopathy

AIMSTo assess the potential role of macrophage migration inhibitory factor (MIF) in the pathogenesis of proliferative diabetic retinopathy (PDR).METHODSMIF levels were assayed in the vitreous and paired serum samples of...