Ocular Safety of Intravitreal Anti Connective Tissue Growth Factor Neutralizing Antibody

To determine the maximum safe dose for intravitreal injection of anti-CTGF (IVAC) in rat eyes in order to decrease gene and protein expression of connective tissue growth factor (CTGF) for the treatment of ocular fibrotic disorders.
Forty-five Lister hooded pigmented rats were divided into one of the five groups of 9 rats; 4 out of these 5 groups received different doses of IVAC (2μl); 10 mg/ml in group B, 20 mg/ml in group C, 50 mg/ml in group D, and 100 mg/ml in group E. The sham group (group A) received 2μl of normal saline. Full field electroretinography (ERG) was performed at baseline and on days 7 and 28 after the IVAC injection. At end of the study, the animals were euthanized and the injected eyes were subjected to routine histopathology, immunohistochemistry for glial fibrillaryacidic protein (GFAP), and terminal transferase dUTP nick end-labeling (TUNEL) assay.
In group E, Baseline scotopic rod b-wave amplitude and maximal combined b-wave amplitude were 111.89±71.2 μv and 178.57 ±55.58 μv, respectively, which significantly reduced to 79.31 ± 52.59 μv and 128.73 ± 41.61 μv, respectively, after 28 days (P ERG, histopathologic, and apoptotic assays revealed no toxic effects of 10 to 50 mg/ml of IVAC in the rat eyes. The injection of 100mg/ml IVAC, however, caused significant deleterious effects on both retinal function and structure as demonstrated by functional tests, and histopathologic and TUNEL findings.