Hyper-Reflecting Foci in Multiple Sclerosis Retina Associate With Macrophage/Microglia-Derived Cytokines in
Marco Puthenparampil1, Tommaso Torresin2, Silvia Franciotta1
1Multiple Sclerosis Centre, Neurology Clinic, Department of Neuroscience, Università degli Studi di Padova, Padova, Italy.
Background:
Increasing evidence suggests that retinal hyper-reflecting foci (HRF) might be clusters of activated and proliferating microglia. Since microglia are widespread activated in multiple sclerosis (MS) brain, its evaluation in retina may help to understand and monitor MS-related pathology.
Aim:
This study aims at investigating the association of HRF with cerebrospinal fluid (CSF) cytokines and MRI parameters in relapsing-remitting MS (RRMS).
Methods:
Nineteen RRMS at clinical onset and 15 non-inflammatory neurological disorders (NIND) underwent brain 3T MRI and CSF examination. Optical coherence tomography (OCT) analysis, including HRF count, was performed on RRMS patients. Sixty-nine cytokines/chemokines were analyzed in the CSF by multiplex technology.
Results:
In RRMS, HRF count in the ganglion cell layer (GCL) was associated with IL-1Ra, IL-9, IL-15, IFN-γ, and G-CSF. Moreover, in RRMS patients CSF concentrations of IL-1Ra and G-CSF associated with global cortical thickness. The HRF count in the inner nuclear layer (INL) correlated with IL-22, IL-34, IL-35, CXCL-2, CXCL-10, and CXCL-13, and multivariate analysis confirmed a strong association (r2: 0.47) with both CXCL-2 (β: -0.965, p = 0.0052) and CXCL-13 (β: 0.241, p = 0.018). This latter cytokine increased in RRMS with high HRF count compared with NIND and RRMS with low HRF count. Finally, the CXCL-13/CXCL-2 ratio strongly associated with HRF count (r: 0.8, p < 0.005) and cortical lesion volume (r: 0.5, p < 0.05).
Conclusions:
The association of HRF with intrathecally produced monocyte/microglia-derived cytokines confirms their microglial origin and indicates they are worth further evaluating as markers of activated microglia.
Insights
Retinal hyper-reflecting foci (HRF) correlate with specific cytokines in cerebrospinal fluid (CSF), suggesting they are markers of activated microglia in multiple sclerosis (MS). This finding may aid in monitoring MS pathology.
Area of Science:
- Neuroimmunology
- Ophthalmology
- Neurology
Background:
- Retinal hyper-reflecting foci (HRF) are proposed to represent activated microglia.
- Microglia activation is a key feature in multiple sclerosis (MS) brain pathology.
- Evaluating retinal HRF could offer insights into MS-related retinal and brain changes.
Purpose of the Study:
- To investigate the association between retinal HRF and cerebrospinal fluid (CSF) cytokines in relapsing-remitting MS (RRMS).
- To explore the relationship between HRF, CSF cytokines, and MRI parameters in RRMS patients.
Main Methods:
- Nineteen RRMS patients and 15 non-inflammatory neurological disorder (NIND) controls underwent brain MRI and CSF analysis.
- Optical coherence tomography (OCT) was used to count HRF in RRMS patients.
- Sixty-nine cytokines/chemokines were quantified in CSF using multiplex technology.
Main Results:
- HRF count in the ganglion cell layer (GCL) correlated with IL-1Ra, IL-9, IL-15, IFN-γ, and G-CSF.
- CSF IL-1Ra and G-CSF levels were associated with global cortical thickness in RRMS.
- HRF count in the inner nuclear layer (INL) correlated with multiple cytokines, notably CXCL-2 and CXCL-13, with a strong multivariate association (r²: 0.47).
- The CXCL-13/CXCL-2 ratio showed strong associations with HRF count (r: 0.8) and cortical lesion volume (r: 0.5).
Conclusions:
- The correlation of HRF with specific CSF cytokines supports their origin from activated microglia.
- HRF may serve as valuable biomarkers for assessing microglial activation in MS.
- Further evaluation of HRF is warranted for monitoring MS pathology.
