PurposeThe ciliary body (CB) of the human eye consists of the non-pigmented (NPE) and pigmented (PE) neuro-epithelia. We investigated the gene expression of NPE and PE, to shed light on the molecular mechanisms underlying the most important functions of the CB. We also developed molecular signatures for the NPE and PE and studied possible new clues for glaucoma.MethodsWe isolated NPE and PE cells from seven healthy human donor eyes using laser dissection microscopy. Next, we performed RNA isolation, amplification, labeling and hybridization against 44×k Agilent microarrays. For microarray conformations, we used a literature study, RT-PCRs, and immunohistochemical stainings. We analyzed the gene expression data with R and with the knowledge database Ingenuity.ResultsThe gene expression profiles and functional annotations of the NPE and PE were highly similar. We found that the most important functionalities of the NPE and PE were related to developmental processes, neural nature of the tissue, endocrine and metabolic signaling, and immunological functions. In total 1576 genes differed statistically significantly between NPE and PE. From these genes, at least 3 were cell-specific for the NPE and 143 for the PE. Finally, we observed high expression in the (N)PE of 35 genes previously implicated in molecular mechanisms related to glaucoma.ConclusionOur gene expression analysis suggested that the NPE and PE of the CB were quite similar. Nonetheless, cell-type specific differences were found. The molecular machineries of the human NPE and PE are involved in a range of neuro-endocrinological, developmental and immunological functions, and perhaps glaucoma.

This is an open access article under the terms of the Creat ive Commo ns Attri butio n-NonCo mmerc ial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. Purpose: To develop an efficient algorithm for multi-component analysis of magnetic resonance fingerprinting (MRF) data without making a priori assumptions about the exact number of tissues or their relaxation properties. Methods: Different tissues or components within a voxel are potentially separable in MRF because of their distinct signal evolutions. The observed signal evolution in each voxel can be described as a linear combination of the signals for each component with a non-negative weight. An assumption that only a small number of components are present in the measured field of view is usually imposed in the interpretation of multi-component data. In this work, a joint sparsity constraint is introduced to utilize this additional prior knowledge in the multi-component analysis of MRF data. A new algorithm combining joint sparsity and non-negativity constraints is proposed and compared to state-of-the-art multi-component MRF approaches in simulations and brain MRF scans of 11 healthy volunteers. Results: Simulations and in vivo measurements show reduced noise in the estimated tissue fraction maps compared to previously proposed methods. Applying the proposed algorithm to the brain data resulted in 4 or 5 components, which could be attributed to different brain structures, consistent with previous multi-component MRF publications. Conclusions: The proposed algorithm is faster than previously proposed methods for multi-component MRF and the simulations suggest improved accuracy and precision of the estimated weights. The results are easier to interpret compared to voxel-wise methods, which combined with the improved speed is an important step toward clinical evaluation of multi-component MRF. K E Y W O R D S joint sparsity constraint, MR fingerprinting, multi-component analysis, NNLS, partial volume effect, Sparsity Promoting Iterative Joint NNLS (SPIJN) 522 | NAGTEGAAL ET AL. | 523 NAGTEGAAL ET AL.

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.