Eye and Brain (Dec 2022)
Neuroplasticity of the Lateral Geniculate Nucleus in Response to Retinal Gene Therapy in a Group of Patients with RPE65 Mutations
Abstract
Manzar Ashtari,1– 3 Mikhail Lipin,1,2 Michelle Duong,4 Gui-Shuang Ying,5 Yinxi Yu,5 Albert Maguire,1,2 Jean Bennett1,2 1Department of Ophthalmology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA; 2Department of Ophthalmology, Center for Advanced Retinal & Ocular Therapeutics (CAROT) at the University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA; 3Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA; 4Emergency Department, Mainline Health, Bryn Mawr, PA, USA; 5Department of Ophthalmology, Center for Preventative Ophthalmology and Biostatistics, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USACorrespondence: Manzar Ashtari, University of Pennsylvania, Perelman School of Medicine, Room 201 Anatomy/Chemistry Building, Philadelphia, PA, 19102, USA, Tel +1 215– 746-8259, Email [email protected]: Previous works on experience-dependent brain plasticity have been limited to the cortical structures, overlooking subcortical visual structures such as the lateral geniculate nucleus (LGN). Animal studies have shown substantial experience dependent plasticity and using fMRI, human studies have demonstrated similar properties in patients with cataract surgery. However, in neither animal nor human studies LGN has not been directly assessed, mainly due to its small size, tissue heterogeneity, low contrast/noise ratio, and low spatial resolution.Methods: Utilizing a new algorithm that markedly improves the LGN visibility, LGN was evaluated in a group of low vision patients before and after retinal intervention to reinstate vision and normal sighted matched controls.Results: Between and within groups comparisons showed that patients had significantly smaller left (p< 0.0001) and right (p < 0.00002) LGN volumes at baseline as compared to the one-year follow-up volumes. The same baseline and one year comparison in controls was not significant. Significant positive correlations were observed between the incremental volume increase after gene therapy of the left LGN and the incremental increase in the right (r = 0.71, p < 0.02) and left (r = 0.72, p = 0.018) visual fields. Incremental volume increase of the right LGN also showed a similar positive slope but did not reach significance.Discussion: These results show that despite significantly less volume at baseline, retinal gene therapy promotes robust expansion and increase in LGN volume. Reinstating vision may have facilitated the establishment of new connections between the retina and the LGN and/or unmasking of the dormant connections. The exact trajectory of the structural changes taking place in LGN is unclear but our data shows that even after years of low vision, the LGN in RPE65 patients has the potential for plasticity and expansion to a nearly normal volume one year after gene therapy administration.Keywords: brain plasticity, retinal gene therapy, lateral geniculate nucleus, image processing, brain morphometry
