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The choroid plexus of the mature and aging rat: the choroidal epithelium.

The choroid plexus of mature and old rats has been examined by both scanning and transmission electron microscopy. It has been shown that the macrophages lying upon the ventricular surface of the choroid plexus have a close association with burr-like protrusions that extend from the apical surfaces of the choroidal epithelial cells. These protrusions have a dark cytoplasm filled with vesicles and tubules, and projecting from them are thin, shrunken microvilli. It is suggested that these protrusions are phagocytosed by the macrophages and that they are the source of some of the inclusions which become increasingly common within the cytoplasm of macrophages in older rats. The lateral surfaces of the choroidal epithelial cells have also been examined in the scanning electron microscope after exposure of the surfaces by dissection. In such preparations it is apparent that the elaborate interdigitations between adjacent cells are effected by irregular and vertically arranged folds confined to the basal portions of the lateral cell surfaces. Lastly, it has been shown that at the junction between the choroid plexus and the ependyma in the lateral ventricle, there are two modes of transition between the choroidal and ependymal epithelia. In one, typical choroidal and ependymal epithelial cells lie next to each other to produce a distinct and continuous bondary. In the other mode the boundary is also continuous, but there are modified ependymal cells present. These modified cells have short, relatively sparsely distributed microvilli and not more than one or two cilia.

Aging

The hypothalamo-choroidal tract. I. Immunohistochemical demonstration of neurophysin pathways to telencephalic choroid plexuses and cerebrospinal fluid.

Neurosecretory pathways were examined in normal male rats by the use of the immunoperoxidase technique for the localization of neurophysin in Bouin-fixed, deparaffinized sections. Using this technique two projections of extrahypothalamic neuorosecretory fibers can be traced to the sites of origin of the choid plexuses of both horns of the lateral ventricles. Neurophysin-containing axons originating primarily from the paraventricular field course dorsolaterad to enter the choroid fissure of the dorsal horn. A caudally direced group of fibers course ventrolaterad to enter the ventral horn choroid fissures. The supraoptic nuclear field is the primary contributor to the latter group. Scattered neurosecretory neurons are found in association with both pathways, usually in contact with blood vessels supplying the choroid plexuses, or in the telencephalic subependymal stroma. Neurosecretory fibers and terminals occur within the choroid fissures and juxtaventricular neuropil. The neurosecretory terminals in the choroid fissures appear as Herring-body type neurohemal organs; in the neuropil they appear as punctate peri-neuronal desities suggestive of synaptic contacts. Thes morphologic findings are discussed in relation to reports indicating the presence of antidiuretic, vasopressin-like activity in cerebrospinal fluid and choroid plexus extraxts together with ultrastructural evidence supportive of vasopressin-mediated transchoroidal cerebrospinal fluid absorption. These results and those of others indicated the possible involvement of the neurosecretory system in the regulation of brain interstitial-ventricular cerebrospinal fluid dynamics.

Animals

Choroidal neovascularization associated with choroidal nevi.

We observed choroidal neovascularization with associated macular detachment in three cases of benign choroidal nevi. Successful obliteration of the neovascular membranes was performed with argon laser photocoagulation with maintenance of good central visual acuity.

Adult

Malignant melanoma of the choroid presenting as choroidal detachment following cataract surgery.

The progression of a monocular nuclear cataract was observed for thirty-two months in an eye which was apparently otherwise normal. Three weeks after uncomplicated cataract surgery the patient presented with an apparent detachment of the choroid which enlarged dramatically within a relatively short time and which was further complicated by a retinal detachment. The subsequent development of rubeosis iridis and increased intraocular pressure suggested some other etiology. Ultrasonography revealed a malignant melanoma which was confirmed following enucleation. Transillumination of all suspected postoperative choroidal detachments is recommended with more definitive examination when indicated.

Aged

[Scintigraphy of the choroid plexus (choroid plexography)].

An increase concentration of pertechnate in the choroid plexus was demonstrated in 21 patients pretreated with tin pyrophosphate injected intravenously 24 hours before the examination. Using this technique, the choroid plexus are seen quite clearly, giving indirectly a picture of the intracerebral ventricles. A dynamic study was carried out in 12 patients, 3 of whom had abnormalities of the cerebrospinal fluid circulation demonstrated by isotope cisternography. The results obtained were characterised by a typical diphasic curve with variations in the pathological cases.

Brain Neoplasms

The human choroid plexus and autoimmune nephritis.

The choroid plexus resembles the glomerular basement membrane (GBM) and may be a site of injury or source of antigen in Goodpasture syndrome. Immunohistologic studies were performed on the choroid plexus of a patient with auto-immune nephritis and pulmonary hemorrhage. The studies showed linear deposition of host IgG, IGM, and beta1c. Antibody eluted from the diseased kidney fixed in a linear pattern to normal choroid plexus and could be absorbed by either choroid plexus or GBM. Antibody to choroid plexus fixed to GBM and the linear staining was no longer observed after absorption with GBM or choroid plexus. Antibody to GBM fixed to normal choroid plexus and was obsorbed by both choroid plexus and glomerular basement membrane. The studies suggest an immunologic relationship between choroid plexus and GBM and a role for the choroid plexus in autoimmune nephritis.

Animals

Distribution of transgene in the rodent choroid plexus after intracerebroventricular injection of adeno-associated virus.

Using adeno-associated virus to transfer genetic information to the choroid plexus has emerged as a promising route for long-term gene therapy in the brain for a variety of conditions. Overexpression of proteins has proved effective in small animal models but few attempts have been made to translate this technology to clinic, suppress the activity of a protein of interest, or further expand the limited capsid serotypes known to have choroid plexus tropism. We utilise transfer of green fluorescent protein to show choroid plexus epithelium tropism for novel AAV6 derived capsid ShH10Y445F in mouse, rat and porcine tissue explant cultures. In vivo tropism is shown in the mouse following stereotactic intracerebroventricular injection. We examined the distribution of viral transduction across the choroid plexus in all four ventricles following a single unilateral intracerebroventricular injection using both green fluorescent protein as a transgene, but also the CRISPR/Cas9 system to deliver permanent knockdown of apical water channel aquaporin-1. Quantitative immunofluorescence and SURVEYOR assay were used to statistically assess the magnitude and extent of choroid plexus knockdown across the ventricular system. We conclude that serotype ShH10Y445F targets choroid plexus epithelium in mouse, rat and pig; and when carrying the CRISPR/Cas9 system can reduce target protein expression in these cells. Transduced choroid plexus epithelial cells distribute unevenly with a bias toward the lateral ventricle on the injected side and a preferential infection of choroid plexus in the lateral over the third and fourth ventricles. Overcoming irregular distribution represents a challenge for clinical translation of this technology where clinical efficacy may require manipulation of the entire choroid plexus.

Animals

Ultrasonographic features of choroidal malignant melanomas.

In a 12-month period 26 eyes were enucleated after an ultrasonographic diagnosis was made of malignant melanoma of the choroid. Histologic features of the tumors were reviewed. The ultrasonographic diagnosis was correct in 100% (26/26) of enucleated eyes. Spontaneous vascular movement (SVM) was identified by standardized A-scan echography in 69% (18/26) of the tumors. Contact B-scan ultrasonography demonstrated choroidal excavation in 65% (17/26) of the melanomas. During the 12-month study period, choroidal excavation was also demonstrated in cases of metastatic choroidal tumors, hemangiomas of the choroid, and long-standing choroidal nevi. The standardized A-scan finding of SVM is a compelling sign in the diagnosis of choroidal malignant melanoma. In contrast, the B-scan finding of choroidal excavation is a less useful sign since it may also be seen in various other ocular lesions.

Aged

Genome-wide discovery reveals 30 loci for choroidal thickness and uncovers potential causal links with angle-closure glaucoma.

The choroid is critical for maintaining vision and implicated in several ocular diseases, being the sole source of nutrients and waste removal for the outer retina. Genetic discovery can help elucidate the pathways through which choroidal features influence disease risk. Our meta-analysis of genome-wide association studies (n= 78,682 participants) identified 30 genomic regions, including 20 novel loci, associated with choroidal thickness. Findings suggest inflammatory and vascular processes drive choroidal thickness, with overlapping mechanisms shared with refractive error. Genome-wide independently significant SNPs accounted for 18.7% of the genetic variance in choroidal thickness. Mendelian randomisation analyses showed a causal effect of age-related macular degeneration on choroidal thickness, and suggest a bidirectional causal effect between choroidal thickness and primary angle-closure glaucoma. These findings provide insight into the shared genetic architecture and biological pathways linking choroidal thickness and related diseases.

Canadian Longitudinal Study on Aging

The natural course of active choroidal lesions in the presumed ocular histoplasmosis syndrome.

Eighty-two patients and 106 eyes with the POHS have been followed for one year or longer. Untreated active choroidal lesions were divided into groupings based on the distance from the center of the CFZ and the reltionship to the border of the CFZ. Twenty-three percent of untreated active choroidal lesions that were located inside the CFZ achieved 20/20 to 20/40 vision. Sixty-three percent of untreated active choroidal lesions that were located outside of the CFZ achieved a vision of 20/20 to 20/40. The active choroidal lesions with the best visual prognosis were 0.25 to 0.5 disc diamterers, demonstrated no growth, and had little or no associated choroidal bleeding. Activation of choroidal lesions in the fellow eye at the site of preexisting atrophic scars was documented in 21% of the eyes. One fellow eye developed a de novo active choroidal lesion. Eighteen percent of the cases had structurally congested nerve heads characterized by slight elevation of the disc and no physiologic depression; 3% of the eyes had drusen of the optic nerve. A relationship may exist between peripapillary scarring in the POHS and these nerve head changes.

Adolescent

Active transport of riboflavin by the isolated choroid plexus in vitro.

In vitro, the transport of [14C]riboflavin into and from the isolated choroid plexus, the anatomical locus of the blood-cerebrospinal fluid barrier, was studied. With concentrations of [14C]riboflavin of 0.7 microM (or greater) in the incubation medium, the choroid plexus accumulated [14C]riboflavin against a large concentration gradient by a process that did not depend on binding or intracellular metabolism of the [14C]riboflavin. The [14C]riboflavin accumulation process in isolated choroid plexus could be described by Michaelis-Menten transport kinetics (kt = 78 microM and Ymax = 1.65 mmol kg-1 (15 min)-1) and was inhibited by other flavins and probenecid but not by ribose, weak bases, or other B vitamins. The accumulation process was markedly depressed by iodoacetate and low temperatures. With a concentration of 0.08 microM [14C]riboflavin in the incubation medium, 28% of the [14C]riboflavin within the choroid plexus was converted to [14C]FAD or [14C]FMN intracellularly. Unlike the active transport of [14C]riboflavin into choroid plexus, accumulated [14C]riboflavin departed choroid plexus by a process independent of intracellular concentration or temperature. The efflux of [14C]riboflavin from choroid plexus could be described by first oder kinetics with a rate constant of -0.08 min-1.

Animals

[Electron microscopic study on the focal immune response in the choroid (author's transl)].

Pigmented rabbits were sensitized by subcutaneous injection of BCG together with Freund's complete adjuvant and heat killed tubercle bacilli together with adjuvant. After the titer of serum antibody to BGG was elevated or tuberculin skin test became positive, choroiditis was induced in these eyes by an injection of BGG or PPD directly through the posterior sclera in the vicinity of the optic nerve. The eyes were enucleated at various intervals and the choroid was studied by light and electron microscopy. In the choroid challenged with BGG, infiltrates such as polymorphonuclear leukocytes and lymphocytes were seen, in early stages, invading in the posterior segment and peripheral area near the ciliary body. These cells decreased in number within a few days, and after one week a few plasma cells were detected in the posterior uvea. In the choroid challenged with PPD, infiltration of monocytes and lymphocytes was seen in early stages, reaching its peak in 48 hours. After 4 and 5 days lymphocytes decreased in number, but monocytes showed mitotic and phagocytotic activity, and accumulated near the sclera. After one week typical epithelioid cells were detected along the suprachoroidal space. These events were restricted within the choroid. The results obtained suggest, that in the focal immune reaction of the choroid, the cellular sequence of events and the range of tissue involved are different depending upon the kinds of antigen used. It may indicate humoral immunity on one side and cell-mediate immunity on the other.

Animals

Retinal and choroidal contribution to retinal metabolism in vivo. A study in pigs.

The glucose metabolism of the retina was studied in vivo, by determining glucose, oxygen and lactate a-v differences for choroidal and retinal blood in pigs at different levels of intraocular pressure. At normal intraocular pressure the choroidal a-v differences were 0.07 and 0.11 mmol/l for glucose and oxygen respectively. The corresponding figures for the retina were 0.44 and 2.15. At increased levels of intraocular pressure the choroidal and retinal glucose and choroidal oxygen a-v differences increased, thus at least partly compensating for reduced blood flow. A major part of the oxygen and glucose consumed by the retina was delivered by the choroid. The total amount of oxygen extracted from choroidal and retinal blood could only account for complete oxidation of 37% of the extracted glucose. The results obtained in determinations of lactate a-v differences indicate that part of the remaining glucose is used for anaerobic glycolysis.

Animals

A morphological study of the development of the mouse choroid plexus.

Development of the mouse choroid plexus was studied by semithin light microscopy, transmission electron microscopy and scanning electron microscopy. The choroid plexus is first observed as a bilateral ridge at 11 days postconception. The major morphological development appears to occur between 11 and 14 days postconception. By 14 days both dark and light choroid plexus epithelial cells are present. The percentage of dark cells appears constant from 14 days postconception up to 3 months postnatum. Metachromatically staining glycogen masses are present in the choroidal epithelium from 13 days postconception until 5 days postnatum, after which time glcogen granules are sparsely scattered throughout the cytoplasm. A few fine microvilli are present at 11 days postconception and these increase in number and become much more bulbous by 13 days. In contrast to the light choroid plexus epithelial cells, the dark cells have fine narrow microvilli. The possible significance of the two types of choroid plexus cells is discussed.

Aging

Electron microscopic demonstration of hormone-producing metastatic carcinoma of the choroid from the bronchus.

Clinical, laboratory and pathological findings of a patient in bronchial carcinoma with choroidal metastasis were presented. X-ray examination of the chest suggested the tumor shadow in the posterior segmental bronchus of the right upper lobe of the lung (r-B2b), while funduscopy and fluorescein angiography revealed the presence of choroidal tumor. ACTH levels in tumor tissues at autopsy and in serum were measured and definitely demonstrated and elevated. Histopathologically, the primary lesion was r-B2b and diagnosed as a mucocellular type of adenocarcinoma. The choroidal lesion was metastatic carcinoma. Electron microscopic examination of the choroidal lesion reembedded for electron microscopy from celloidin-embedded materials for light microscopy could reveal the presence of characteristic cytoplasmic granules referred to as neurosecretory-type granules. It is extremely rare that a hormone-producing metastatic carcinoma of the choroid from the bronchus has been proved.

Adenocarcinoma