Intravitreal Panitumumab and Retinal Pigment Epithelium Proliferation in Laser-Induced Retinal Degeneration in Rabbits

Mukharram M. Bikbov¹Gyulli Kazakbaeva¹Songhomitra Panda-Jonas²Iskander D Valishin¹Aigul M Nizamutdinova¹Jost B Jonas^{3,4,5,6,7,8,9*}

• ¹Ufa Eye Research Institute, Ufa, Russia
• ²Universitat Heidelberg, Heidelberg, Germany
• ³Hopital Rothschild, Paris, France
• ⁴Singapore Eye Research Institute, Singapore, Singapore
• ⁵LV Prasad Eye Institute, Hyderabad, India
• ⁶Beijing Tsinghua Changgung Hospital, Beijing, China
• ⁷The Chinese University of Hong Kong, Hong Kong, Hong Kong, SAR China
• ⁸Privatpraxis Prof Jonas und Dr Panda-Jonas, Heidelberg, Germany
• ⁹New York Eye and Ear Infirmary of Mount Sinai Ophthalmology, New York, United States

Purpose: To examine the effect of intravitreally applied epidermal growth factor (EGF) receptor blocker panitumumab on proliferation of retinal pigment epithelium cells (RPE) in an experimental model of localized retinal degeneration. Methods: The experimental study included rabbits with an age of 2 to 3 months and a body weight of 2.5 to -3 kg and which were randomly distributed into a study group and control group. The right eyes received two retinal argon laser coagulation spots (500 mWatt; diameter:100μm; duration:0.5s), applied with an interval of two minutes at the same location close to the vascular streak in the posterior fundus region. Five times in two-day intervals, the rabbits of the study group received intravitreal injections of 1 mg panitumumab (0.10 mL) and the rabbits of the control group intravitreal injections of 0.10 mL Ringer´s solution. At baseline, at each time point of re-examination, and at study end, the animals were examined by fundus photography and optical coherence tomography of the laser spot. Results: The study included 19 rabbits (study group: 10 animals; control group: 9 animals). After the third injection and at study end, the laser-induced area of depigmentation+hyperpigmentation combined did not vary significantly between the study group and control group (1.43±0.63 mm2 versus 1.63±0.77 mm2; P=0.56; and 1.37±0.63 mm2 versus 1.61±0.74 mm2; P=0.46, respectively). At the same time points, the area with hyperpigmentation was significantly smaller in the study group than control group (0.16±0.15 mm2 versus 0.80±0.59 mm2; P=0.01; and 0.14±0.14 mm2 versus 0.70±0.56 mm2; P=0.02, respectively). At the same time points, the ratio of the hyperpigmented area to the combined depigmented+hyperpigmented area was significantly smaller in the study group than control group (0.11±0.09 versus 0.43±0.19mm2; P<0.001; and 0.10±0.08 versus 0.35±0.23mm2; P=0.006, respectively)Conclusions: These findings indicate that intravitreally administered panitumumab was associated with reduced subretinal hyperpigmentation in a laser-induced model of retinal injury. While this may reflect a modulation of the RPE response, including potential suppression of RPE proliferation, further studies incorporating histological and molecular analyses are warranted to confirm its effect on subretinal fibrosis.