Abstract:
Purpose:The purpose of this prospective experimental study was to evaluate the safety/toxicity of α4β1 integrin blockade in rabbit retina using its monoclonal antibody (Natalizumab). Methods:Twelve New Zealand albino rabbits were divided into three groups (n = 4). Unilateral intravitreal injections of three different concentrations of natalizumab were performed in every rabbit of each group (Group A: 0.625 mg, Group B: 1.25 mg, and Group C: 2.5 mg). Baseline electroretinogram (ERG) and fundus photography were performed prior to injection. At days 1, 7, and 21 postinjection, ERG and fundus photography of each eye were performed. At last follow-up, Group C animals with highest drug concentration were sacrificed and the enucleated eyes were evaluated for retinal toxicity using transmission electron microscopy (TEM). Results:No difference in ERG responses was observed in eyes injected with low and intermediate concentration of natalizumab between day 0 and day 21. Furthermore, rabbits injected intravitreally with highest dose showed reduction in amplitude of "a" wave (P = 0.0017) and a reduction in amplitude of "b" wave of ERG at day 21 (P = 0.0117). TEM revealed changes in the outer plexiform layer and inner nuclear layer, suggestive of toxicity primarily to the photoreceptor synaptic terminals and bipolar cells. Conclusion:Low-dose (0.625 mg) and intermediate-dose (1.25 mg) intravitreal injection of natalizumab appears safe for rabbit retina. However, functional and anatomical changes were observed in rabbit retina following a high-dose (2.5 mg) intravitreal injection of a monoclonal antibody blocking α4β1 integrin.
journal_name
Indian J Ophthalmoljournal_title
Indian journal of ophthalmologyauthors
Chawla R,Nath M,Moksha L,Nag TC,Velpandian Tdoi
10.4103/ijo.IJO_425_18subject
Has Abstractpub_date
2018-10-01 00:00:00pages
1441-1445issue
10eissn
0301-4738issn
1998-3689pii
IndianJOphthalmol_2018_66_10_1441_242012journal_volume
66pub_type
杂志文章abstract::Since the year 2000, the amount written about the economics of blindness and visual impairment has increased substantially. In some cases, the studies listed under this heading are calculations of the costs related to vision impairment and blindness at a national or global level; in other cases the studies examine the...
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