The development of the nervous and vascular systems constitutes primary events in the evolution of the animal kingdom; the former provides electrical stimuli and coordination, while the latter supplies oxygen and nutrients. Both systems have more in common than originally anticipated. Perhaps the most striking observation is that angiogenic factors, when deregulated, contribute to various neurological disorders, such as neurodegeneration, and might be useful for the treatment of some of these pathologies. The prototypic example of this cross-talk between nerves and vessels is the vascular endothelial growth factor or VEGF. Although originally described as a key angiogenic factor, it is now well established that VEGF also plays a crucial role in the nervous system. We describe the molecular properties of VEGF and its receptors and review the current knowledge of its different functions and therapeutic potential in the nervous system during development, health, disease and in medicine.

Role and Therapeutic Potential of VEGF in the Nervous System

Macular telangiectasia type 2

Animal models of choroidal and retinal neovascularization.

The archetypal vascular endothelial growth factor, VEGF, arose in evolution as a signal affecting neural cells, and was subsequently co-opted to regulate vascular function. Here, the authors review the roles of the VEGF family as both aetiological factors and therapeutic targets in neurological disease.

Vascular endothelial growth factor: a neurovascular target in neurological diseases.

Microglial changes occur without neural cell death in diabetic retinopathy

EPH236 Hospitalizations Related to Cytopenias Among the Multiple Myeloma Adult Inpatient Population in the United States

To investigate the relationship between ophthalmic artery (OA) blood flow parameters and retinal nerve fiber layer (RNFL) thickness in eyes with pseudoexfoliation (PEX).We compared PEX eyes without glaucoma (group A, n = 53) and those with glaucoma (group B, n = 18) with control eyes (group C, n = 44). Subsequently, eyes in groups A and B were compared. Finally, OA color Doppler imaging measurements were recorded, and peripapillary RNFL analysis was performed.The total RNFL measurements differed significantly among the groups (P = 0.012), being thicker in group C than in group A (P = 0.010) and significantly different between group B and groups A and C (both P = 0.001). The peak systolic velocity (PSV) and end diastolic velocity (EDV) measurements of groups A and B were lower than those of group C (PSV: P = 0.001 and P = 0.001, respectively; EDV: P = 0.001 and P = 0.001, respectively). No significant difference was noted in resistive index (RI) measurements (P = 0.370). In group B, significant negative correlations were noted between total RNFL and PSV (r = –0.743; P = 0.001) and between total RNFL and EDV (r = –0.691; P = 0.001), but not between total RNFL and RI measurements (P = 0.548).Pseudoexfoliation syndrome (PXS) with or without glaucoma was associated with a decrease in the PSV and EDV values of the OA. An extensive study may be needed to further explore the role of PXS in OA blood flow parameters. Total RNFL thickness values were lower in eyes with PEX than in those without.Étudier le lien entre les paramètres du débit sanguin de l’artère ophtalmique (AO) et l’épaisseur de la couche des fibres nerveuses rétiniennes (CFNR) dans les yeux présentant une pseudo-exfoliation (PEX).Nous avons comparé des yeux PEX sans glaucome (groupe A, n = 53) et avec glaucome (groupe B, n = 18) avec des yeux témoins (groupe C, n = 44). Par la suite, les yeux des groupes A et B ont été comparés entre eux. Enfin, des relevés d’imagerie Doppler Couleur de l’AO et une analyse de la CFNR péripapillaire ont été effectués.Les relevés de la CFNR totale présentaient des différences significatives selon les groupes (p = 0,001). Ils étaient plus élevés dans le groupe C que dans le groupe A (p = 0,010) et présentaient des différences significatives entre les groupes B et C (p = 0,001). Les relevés de la vitesse maximale systolique (VMS) et de la vitesse diastolique finale (VDF) dans les groupes A et B étaient inférieurs à ceux du groupe C (respectivement p = 0,007 et p = 0,001; respectivement p = 0,004 et p = 0,001).Le syndrome de pseudo-exfoliation (SPE) avec ou sans glaucome a été associé à une diminution des valeurs VMS et VDF de l’AO. Une étude plus approfondie peut être nécessaire pour explorer davantage le rôle du SPE dans les paramètres du débit sanguin de l’AO. Les valeurs de l’épaisseur totale de la CFNR étaient réduites dans les yeux présentant une PEX. 

Graft dislocation into the vitreous cavity.

Aim: To generate a mouse model for slow progressive retinal neovascularisation through vascular endothelial growth factor (VEGF) upregulation.

Methods: Transgenic mice were generated via microinjection of a DNA construct containing the human VEGF165 (hVEGF) gene driven by a truncated mouse rhodopsin promoter. Mouse eyes were characterised clinically and histologically and ocular hVEGF levels assayed by ELISA.

Results: One transgenic line expressing low hVEGF levels showed mild clinical changes such as focal fluorescein leakage, microaneurysms, venous tortuosity, capillary non-perfusion and minor neovascularisation, which remained stable up to 3 months postnatal. Histologically, there were some disturbance and thinning of inner and outer nuclear layers, with occasional focal areas of neovascularisation. By contrast, three other lines expressing high hVEGF levels presented with concomitantly severe phenotypes. In addition to the above, clinical features included extensive neovascularisation, haemorrhage, and retinal detachment; histologically, focal to extensive areas of neovascularisation associated with retinal folds, cell loss in the inner and outer nuclear layers, and partial retinal detachment were common.

Conclusions: The authors generated four hVEGF overexpressing transgenic mouse lines with phenotypes ranging from mild to severe neovascularisation. These models are a valuable research tool to study excess VEGF related molecular and cellular changes and provide additional opportunities to test anti-angiogenic therapies.

https://bjo.bmj.com/content/bjophthalmol/89/7/911.full.pdf

Generation of transgenic mice with mild and severe retinal neovascularisation.

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EPH236 Hospitalizations Related to Cytopenias Among the Multiple Myeloma Adult Inpatient Population in the United States

Graft dislocation into the vitreous cavity.

Generation of transgenic mice with mild and severe retinal neovascularisation.