PRDX2 silencing alleviates reactive hyperplasia of Müller glial cells in diabetic retinopathy by inhibiting the RhoA/ROCK signaling pathway

Table 1 Clinical characteristics of the patients

Variables	Normal (n = 47)	DM (n = 173)	NDR (n = 51)	NPDR (n = 44)	PDR (n = 78)	P value1	P value2
Age (year)	64 (58-73)	63 (53-70)	66 (60-73)	67 (58-70.75)	55 (49.75-62.25)	0.297	0.0001
Females	30 (63.83)	79 (45.7)	24 (47.06)	23 (52.27)	32 (41.03)	0.032	0.095
Hypertension	14 (29.79)	102 (59)	30 (58.82)	28 (63.64)	44 (56.41)	0.0005	0.004
FBG (mmol/L)	5.7 (5.3-6.4)	8.1 (7-9.9)	7.9 (6.9-9.1)	7.9 (7.025-9.8)	8.850 (7.15-11.43)	0.0002	0.0002
ALT (U/L)	16 (14-22)	17 (14-25.25)	18 (14-28.75)	17 (12-19)	17 (14-26.5)	0.276	0.197
AST (U/L)	21.5 (19-24)	19 (15-24)	21 (16-24)	19 (15-22.75)	18.5 (14.75-25.52)	0.008	0.052
ALP (U/L)	74 (62-92)	76 (61.75-90)	71 (56-90)	77 (64-90)	77 (62-90.25)	0.773	0.804
GGT (U/L)	19 (14.5-29.5)	20 (16-33)	28 (19.25-36)	22 (16-37)	19 (14-30.5)	0.311	0.015
TP (g/L)	71 (69-75)	71 (67-74)	71 (68.25-74)	71 (67-74.75)	71 (66-74)	0.286	0.381
Alb (g/L)	45 (43-46)	44 (41-46)	45 (43-47)	43.5 (41.25-46.75)	43 (40.25-45)	0.021	< 0.0001
A/G	1.7 (1.575-1.8)	1.6 (1.4-1.8)	1.7 (1.5-1.875)	1.6 (1.5-1.7)	1.55 (1.4-1.7)	0.042	0.018
K (mmol/L)	4.2 (4.1-4.4)	4.4 (4.2-4.7)	4.3 (4.15-4.5)	4.4 (4.075-4.7)	4.5 (4.2-2.75)	0.027	0.058
Na (mmol/L)	141 (140-142)	140 (139-141)	140 (139-141)	140 (139-141)	140 (139-141)	0.005	0.048
Cl (mmol/L)	105 (104-106)	104 (102-106)	104 (102-106.5)	104 (102-106)	105 (103-106)	0.143	0.419
P (mmol/L)	1.18 (1.085-1.33)	1.21 (1.12-1.36)	1.145 (1.085-1.293)	1.25 (1.04-1.36)	1.25 (1.14-1.40)	0.506	0.067
Ca (mmol/L)	2.374 ± 0.05416	2.373 ± 0.00872	2.405 ± 0.1060	2.37 ± 0.1024	2.353 ± 0.1146	0.779	0.037
Urea (mmol/L)	5.29 (4.56-6.63)	6.14 (4.99-8.4)	5.825 (4.285-7.21)	5.38 (4.863-9.203)	7.415 95.47-9.045)	0.011	0.001
SUA (mmol/L)	301 (256-373)	347 (284-423)	340 (282.5-416.5)	359 (287-423)	349 (275-433.5)	0.01	0.066
SCr (μmol/L)	67 (60-74)	75 (63.75-91.25)	71 (63-89.25)	72.5 (62.75-86.25)	78 (64.75-101.5)	0.002	0.005
VEGFA (pg/mL)	233.8 (181.8-302.6)	273.63 (203.84-358.34)	237.7 (167.6-360.5)	237.1 (204.5-297.8)	308.6 (228.8-399.8)	0.009	0.0001
PRDX2 (pg/mL)	128.6 (46.27-228.5)	189.21 (96.42-259.31)	180.8 (69.9-236.4)	103.4 (33.57-232.7)	225.6 (164.7-322.5)	0.024	0.0001

¹P value for diabetes mellitus group vs normal group.

²P value for the diabetic retinopathy subgroups vs non-diabetic retinopathy group.

Continuous variables are presented as median (interquartile range) or mean ± SD. Categorical variables are presented as n (%). FBG: Fasting blood glucose; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; ALP: Alkaline phosphatase; GGT: Gamma-glutamyl transferase; TP: Total protein; Alb: Albumin; A/G: Albumin/globulin; SCr: Serum creatinine; SUA: Serum uric acid; VEGFA: Vascular endothelial growth factor A; DM: Diabetes mellitus; NDR: Non-diabetic retinopathy; NPDR: Non-proliferative diabetic retinopathy; PDR: Proliferative diabetic retinopathy.

Table 2 Correlation analysis for PRDX2 in patients with diabetes

Variable	Spearman, rs	P value
Age	-0.083	0.278
Females	0.013	0.863
Hypertension	0.038	0.620
FBG	-0.022	0.775
ALT	-0.027	0.728
AST	-0.044	0.582
ALP	0.085	0.287
GGT	-0.138	0.096
TP	-0.051	0.515
Alb	-0.081	0.298
A/G	-0.074	0.345
K	-0.005	0.950
Na	0.056	0.476
Cl	0.075	0.332
P	0.070	0.384
Ca	-0.061	0.442
Urea	0.195	0.011
SUA	0.088	0.264
SCr	0.144	0.061
VEGFA	0.356	< 0.0001
The severity of DR	0.267	< 0.0001

Spearman correlation between plasma PRDX2 levels and non-normally distributed clinical variables in the diabetic cohort. FBG: Fasting blood glucose; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; ALP: Alkaline phosphatase; GGT: Gamma-glutamyl transferase; TP: Total protein; Alb: Albumin; A/G: Albumin/globulin; SCr: Serum creatinine; SUA: Serum uric acid; VEGFA: Vascular endothelial growth factor A; DR: Diabetic retinopathy.

Table 3 Multivariable logistic regression for proliferative diabetic retinopathy risk prediction

Parameter	aOR (95%CI)	P value
Model 1	9.822 (4.012-24.049)	< 0.0001
Model 2	9.097 (2.819-29.355)	0.0002

Binary logistic regression analysis including PRDX2 as a categorized binary variable using the cutoff value of 124.3 pg/mL. PRDX2 was assigned a value of 0 in 25 patients with PRDX2 ≤ 124.3 pg/mL and a value of 1 in 80 patients with PRDX2 > 124.3 pg/mL. Model 1: No modification variables. Model 2: Adjusts for age, hypertension, vascular endothelial growth factor A, fasting blood glucose, serum albumin, albumin/globulin, gamma-glutamyl transpeptidase, serum creatinine, and serum urea. aOR: Adjusted odds ratio; 95%CI: 95% confidence interval.