Mechanisms of Inflammation in Proliferative Vitreoretinopathy: From Bench to Bedside

Table 1

Outcomes of therapeutic agents used in animals to prevent proliferative vitreoretinopathy (PVR).

Agent(s)	Dose and target	In vivo model	Treatment groups	Outcomes	Ref.
ARC126, ARC127, ARC128	20 μg,; aptamers  against; PDGF-B	Rho/PDGFB transgenic mice treated on P7, sacrificed P12	Intravitreal inj. on; P7: PBS OD; ARC126, ARC-127, ARC128 OS	PBS: mean area of GSA+ cells 1.82 mm^2, 11/19 totRD, 4/19 pRD, 79% RD; ARC126: mean area of GSA+ cells 0.79 mm^2 (𝑃=0.0003*), 0 totRD, 1/6 pRD,; 17% RD; ARC127: mean area of GSA+ cells 0.55 mm^2 (𝑃=0.0001*), 0/7 totRD and pRD,; 0% RD; ARC128: mean area of GSA+ cells 2.00 mm^2 (𝑃>0.05), 3/6 totRD, 2/6 pRD, 83% RD	[61]
(a) Mouse mAb IgG1 HH1-57; (b) Trap PDGFRα-Fc5	(a) 200 μg,; inhibits PDGF-C (b) 386 μg,; inhibits all; PDGF isoforms	Rabbits with OD PVR-induced by injection of PRP and fibroblasts	Intravitreal inj. on day 0: control (𝑛=8) versus (a) mAb IgG1 HH1-57 (𝑛=9) and (b) Trap (𝑛=13)	Control:  1Stage1,  2S2,  4S3,  1S4  (day  3);  1Stage2,  2S3,  5S4  (d5);  1Stage2,  1S3,  6S4  (d7); (a) HH1-57: 2S1,  2S2,  4S3,  1S4 (d3, 𝑃=0.229); 2S2,   4S3,  3S4 (d5,  𝑃=0.108); 2S2,3S3,  3S4,  1S5 (d7,  𝑃=0.406); (b) Trap: 1S0,  6S1,  4S2,  1S3,  1S4 (d3,  𝑃=0.041*); 3S1,  3S2,  4S3,  3S4 (d5,  𝑃=0.063); 4S1,  2S2,  3S3,  4S4 (d7,  𝑃=0.058)	[25]
N-acetyl-cysteine (NAC)	10 mmol/L,; reduces ROS levels	Rabbits with OD PVR-induced by injection of PRP and fibroblasts	Intravitreal inj. on days 0, 2, 4, and 7: control (𝑛=10) versus NAC (𝑛=10)	Control: 2Stage0,  8S1 (d1); 1S0,  7S1,  2S2 (d3); 8S1,  1S2,  1S4 (d5); 5S1,  2S2,  2S3,  1S4 (d7); S1,  3S2,  2S3,  1S4,  1S5 (d14); 4S1,  2S2,  1S3,  1S4,  2S5 (d21); 3S1,  3S2,  1S4,  3S5 (d28); 2.6x ↑ phosphorylation of PDGFR in membranes of control compared to NAC; NAC: 8S0,2S1 (d1, 𝑃=0.0232*); 9S0,1S1 (d3, 𝑃=0.0011*); 9S0,1S1 (d5 𝑃=0.0007*); 7S0,3S1 (d7, 𝑃=0.0015*); 4S0,6S1 (d14, 𝑃<0.0011*); 3S0,5S1,2S2 (d21, 𝑃<0.032*); 3S0,4S1,3S2 (d28, 𝑃<0.0185*); no progression to RD	[62]
Minimum neutralizing antibody set (MNAS)	Antibody set against PDGFs, TGFα, EGF, HGF, FGF-2, TGFβ, IL-8, and IGF-1	Rabbits with OD PVR-induced by injection of PRP and fibroblasts	Intravitreal inj. on day 0: control (𝑛=12) versus; MNAS (𝑛=12)	Control: 4/12 (33%) stage 2 PVR, 8/12 (67%) stage 3 PVR or higher with RD; MNAS: 3/12 (25%) no pathology, 5/12 (42%) epiretinal membrane,; 4/12 (33%) stage 2 PVR, no RD	[63]

PDGF: platelet-derived growth factor. ARC128: nonfunctional version of ARC127. P7: postnatal day 7. P12: postnatal day 12. inj.: injection. PBS: phosphate-buffered saline. OD: right eye. OS: left eye. GSA+ cells: ectopic cells in the inner retina staining positive for Griffonia simplicifolia lectin. totRD: total, pRD: partial, RD: retinal detachment. *statistically significant difference compared to control. mAb: monoclonal antibody. PDGFR: platelet-derived growth factor receptor. PRP: platelet-rich plasma. #S0–#S5: number of cases observed at a given Fastenberg Stage of PVR 0–5. d: day. ROS: reactive oxygen species. TGFα: transforming growth factor α. EGF: epidermal growth factor. HGF: hepatocyte growth factor. FGF-2: fibroblast growth factor 2. TGFβ: transforming growth factor β. IL-8: interleukin 8. IGF-1: insulin-like growth factor-1. Ref: Reference number.